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Theses & Dissertations: Cancer Research

Theses/dissertations from 2024 2024.

Novel Spirocyclic Dimer (SpiD3) Displays Potent Preclinical Effects in Hematological Malignancies , Alexandria Eiken

Chemotherapy-Induced Modulation of Tumor Antigen Presentation , Alaina C. Larson

Dying Right: Supporting Anti-Cancer Therapy Through Immunogenic Cell Death , Elizabeth Schmitz

Therapeutic Effects of BET Protein Inhibition in B-cell Malignancies and Beyond , Audrey L. Smith

Targeting KSR1 to inhibit stemness and therapy resistance , Heidi M. Vieira

Identifying the Molecular Determinants of Lung Metastatic Adaptation in Prostate Cancer , Grace M. Waldron

Identification of Mitotic Phosphatases and Cyclin K as Novel Molecular Targets in Pancreatic Cancer , Yi Xiao

Theses/Dissertations from 2023 2023

Development of Combination Therapy Strategies to Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors , Nicholas Mullen

Overcoming Resistance Mechanisms to CDK4/6 Inhibitor Treatment Using CDK6-Selective PROTAC , Sarah Truong

Theses/Dissertations from 2022 2022

Omics Analysis in Cancer and Development , Emalie J. Clement

Investigating the Role of Splenic Macrophages in Pancreatic Cancer , Daisy V. Gonzalez

Polymeric Chloroquine in Metastatic Pancreatic Cancer Therapy , Rubayat Islam Khan

Evaluating Targets and Therapeutics for the Treatment of Pancreatic Cancer , Shelby M. Knoche

Characterization of 1,1-Diarylethylene FOXM1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells , Cassie Liu

Novel Mechanisms of Protein Kinase C α Regulation and Function , Xinyue Li

SOX2 Dosage Governs Tumor Cell Identity and Proliferation , Ethan P. Metz

Post-Transcriptional Control of the Epithelial-to-Mesenchymal Transition (EMT) in Ras-Driven Colorectal Cancers , Chaitra Rao

Use of Machine Learning Algorithms and Highly Multiplexed Immunohistochemistry to Perform In-Depth Characterization of Primary Pancreatic Tumors and Metastatic Sites , Krysten Vance

Characterization of Metastatic Cutaneous Squamous Cell Carcinoma in the Immunosuppressed Patient , Megan E. Wackel

Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling , Pauline Xu

Phos-Tag-Based Screens Identify Novel Therapeutic Targets in Ovarian Cancer and Pancreatic Cancer , Renya Zeng

Theses/Dissertations from 2021 2021

Functional Characterization of Cancer-Associated DNA Polymerase ε Variants , Stephanie R. Barbari

Pancreatic Cancer: Novel Therapy, Research Tools, and Educational Outreach , Ayrianne J. Crawford

Apixaban to Prevent Thrombosis in Adult Patients Treated With Asparaginase , Krishna Gundabolu

Molecular Investigation into the Biologic and Prognostic Elements of Peripheral T-cell Lymphoma with Regulators of Tumor Microenvironment Signaling Explored in Model Systems , Tyler Herek

Utilizing Proteolysis-Targeting Chimeras to Target the Transcriptional Cyclin-Dependent Kinases 9 and 12 , Hannah King

Insights into Cutaneous Squamous Cell Carcinoma Pathogenesis and Metastasis Using a Bedside-to-Bench Approach , Marissa Lobl

Development of a MUC16-Targeted Near-Infrared Antibody Probe for Fluorescence-Guided Surgery of Pancreatic Cancer , Madeline T. Olson

FGFR4 glycosylation and processing in cholangiocarcinoma promote cancer signaling , Andrew J. Phillips

Theses/Dissertations from 2020 2020

Cooperativity of CCNE1 and FOXM1 in High-Grade Serous Ovarian Cancer , Lucy Elge

Characterizing the critical role of metabolic and redox homeostasis in colorectal cancer , Danielle Frodyma

Genomic and Transcriptomic Alterations in Metabolic Regulators and Implications for Anti-tumoral Immune Response , Ryan J. King

Dimers of Isatin Derived Spirocyclic NF-κB Inhibitor Exhibit Potent Anticancer Activity by Inducing UPR Mediated Apoptosis , Smit Kour

From Development to Therapy: A Panoramic Approach to Further Our Understanding of Cancer , Brittany Poelaert

The Cellular Origin and Molecular Drivers of Claudin-Low Mammary Cancer , Patrick D. Raedler

Mitochondrial Metabolism as a Therapeutic Target for Pancreatic Cancer , Simon Shin

Development of Fluorescent Hyaluronic Acid Nanoparticles for Intraoperative Tumor Detection , Nicholas E. Wojtynek

Theses/Dissertations from 2019 2019

The role of E3 ubiquitin ligase FBXO9 in normal and malignant hematopoiesis , R. Willow Hynes-Smith

BRCA1 & CTDP1 BRCT Domainomics in the DNA Damage Response , Kimiko L. Krieger

Targeted Inhibition of Histone Deacetyltransferases for Pancreatic Cancer Therapy , Richard Laschanzky

Human Leukocyte Antigen (HLA) Class I Molecule Components and Amyloid Precursor-Like Protein 2 (APLP2): Roles in Pancreatic Cancer Cell Migration , Bailee Sliker

Theses/Dissertations from 2018 2018

FOXM1 Expression and Contribution to Genomic Instability and Chemoresistance in High-Grade Serous Ovarian Cancer , Carter J. Barger

Overcoming TCF4-Driven BCR Signaling in Diffuse Large B-Cell Lymphoma , Keenan Hartert

Functional Role of Protein Kinase C Alpha in Endometrial Carcinogenesis , Alice Hsu

Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer , Beth Neilsen

Elucidating the Roles of Lunatic Fringe in Pancreatic Ductal Adenocarcinoma , Prathamesh Patil

Theses/Dissertations from 2017 2017

Metabolic Reprogramming of Pancreatic Ductal Adenocarcinoma Cells in Response to Chronic Low pH Stress , Jaime Abrego

Understanding the Relationship between TGF-Beta and IGF-1R Signaling in Colorectal Cancer , Katie L. Bailey

The Role of EHD2 in Triple-Negative Breast Cancer Tumorigenesis and Progression , Timothy A. Bielecki

Perturbing anti-apoptotic proteins to develop novel cancer therapies , Jacob Contreras

Role of Ezrin in Colorectal Cancer Cell Survival Regulation , Premila Leiphrakpam

Evaluation of Aminopyrazole Analogs as Cyclin-Dependent Kinase Inhibitors for Colorectal Cancer Therapy , Caroline Robb

Identifying the Role of Janus Kinase 1 in Mammary Gland Development and Breast Cancer , Barbara Swenson

DNMT3A Haploinsufficiency Provokes Hematologic Malignancy of B-Lymphoid, T-Lymphoid, and Myeloid Lineage in Mice , Garland Michael Upchurch

Theses/Dissertations from 2016 2016

EHD1 As a Positive Regulator of Macrophage Colony-Stimulating Factor-1 Receptor , Luke R. Cypher

Inflammation- and Cancer-Associated Neurolymphatic Remodeling and Cachexia in Pancreatic Ductal Adenocarcinoma , Darci M. Fink

Role of CBL-family Ubiquitin Ligases as Critical Negative Regulators of T Cell Activation and Functions , Benjamin Goetz

Exploration into the Functional Impact of MUC1 on the Formation and Regulation of Transcriptional Complexes Containing AP-1 and p53 , Ryan L. Hanson

DNA Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent of Error-Prone Synthesis, and the Role of dNTP Pools , Olga V. Kochenova

Defining the Role of Phosphorylation and Dephosphorylation in the Regulation of Gap Junction Proteins , Hanjun Li

Molecular Mechanisms Regulating MYC and PGC1β Expression in Colon Cancer , Jamie L. McCall

Pancreatic Cancer Invasion of the Lymphatic Vasculature and Contributions of the Tumor Microenvironment: Roles for E-selectin and CXCR4 , Maria M. Steele

Altered Levels of SOX2, and Its Associated Protein Musashi2, Disrupt Critical Cell Functions in Cancer and Embryonic Stem Cells , Erin L. Wuebben

Theses/Dissertations from 2015 2015

Characterization and target identification of non-toxic IKKβ inhibitors for anticancer therapy , Elizabeth Blowers

Effectors of Ras and KSR1 dependent colon tumorigenesis , Binita Das

Characterization of cancer-associated DNA polymerase delta variants , Tony M. Mertz

A Role for EHD Family Endocytic Regulators in Endothelial Biology , Alexandra E. J. Moffitt

Biochemical pathways regulating mammary epithelial cell homeostasis and differentiation , Chandrani Mukhopadhyay

EPACs: epigenetic regulators that affect cell survival in cancer. , Catherine Murari

Role of the C-terminus of the Catalytic Subunit of Translesion Synthesis Polymerase ζ (Zeta) in UV-induced Mutagensis , Hollie M. Siebler

LGR5 Activates TGFbeta Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

LGR5 Activates TGFβ Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

Theses/Dissertations from 2014 2014

Genetic dissection of the role of CBL-family ubiquitin ligases and their associated adapters in epidermal growth factor receptor endocytosis , Gulzar Ahmad

Strategies for the identification of chemical probes to study signaling pathways , Jamie Leigh Arnst

Defining the mechanism of signaling through the C-terminus of MUC1 , Roger B. Brown

Targeting telomerase in human pancreatic cancer cells , Katrina Burchett

The identification of KSR1-like molecules in ras-addicted colorectal cancer cells , Drew Gehring

Mechanisms of regulation of AID APOBEC deaminases activity and protection of the genome from promiscuous deamination , Artem Georgievich Lada

Characterization of the DNA-biding properties of human telomeric proteins , Amanda Lakamp-Hawley

Studies on MUC1, p120-catenin, Kaiso: coordinate role of mucins, cell adhesion molecules and cell cycle players in pancreatic cancer , Xiang Liu

Epac interaction with the TGFbeta PKA pathway to regulate cell survival in colon cancer , Meghan Lynn Mendick

Theses/Dissertations from 2013 2013

Deconvolution of the phosphorylation patterns of replication protein A by the DNA damage response to breaks , Kerry D. Brader

Modeling malignant breast cancer occurrence and survival in black and white women , Michael Gleason

The role of dna methyltransferases in myc-induced lymphomagenesis , Ryan A. Hlady

Design and development of inhibitors of CBL (TKB)-protein interactions , Eric A. Kumar

Pancreatic cancer-associated miRNAs : expression, regulation and function , Ashley M. Mohr

Mechanistic studies of mitochondrial outer membrane permeabilization (MOMP) , Xiaming Pang

Novel roles for JAK2/STAT5 signaling in mammary gland development, cancer, and immune dysregulation , Jeffrey Wayne Schmidt

Optimization of therapeutics against lethal pancreatic cancer , Joshua J. Souchek

Theses/Dissertations from 2012 2012

Immune-based novel diagnostic mechanisms for pancreatic cancer , Michael J. Baine

Sox2 associated proteins are essential for cell fate , Jesse Lee Cox

KSR2 regulates cellular proliferation, transformation, and metabolism , Mario R. Fernandez

Discovery of a novel signaling cross-talk between TPX2 and the aurora kinases during mitosis , Jyoti Iyer

Regulation of metabolism by KSR proteins , Paula Jean Klutho

The role of ERK 1/2 signaling in the dna damage-induced G2 , Ryan Kolb

Regulation of the Bcl-2 family network during apoptosis induced by different stimuli , Hernando Lopez

Studies on the role of cullin3 in mitosis , Saili Moghe

Characteristics of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer and Ewing's sarcoma , Haley Louise Capek Peters

Structural and biophysical analysis of a human inosine triphosphate pyrophosphatase polymorphism , Peter David Simone

Functions and regulation of Ron receptor tyrosine kinase in human pancreatic cancer and its therapeutic applications , Yi Zou

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Advances in Ovarian Cancer Research

An ovarian tumor grown in a mouse using human cells. Special techniques were used to create the high-resolution, 3-D view of the cancer’s cell structure and inner workings.

The most common ovarian cancers are those that begin in the epithelial cells that line the fallopian tubes or  ovaries . These, along with cancers that form in the peritoneum , are called epithelial ovarian cancers . Other types of ovarian cancer arise in other cells, including germ cell tumors , which start in the cells that make eggs, and stromal cell tumors , which start in supporting tissues. 

NCI-funded researchers are working to advance our understanding of how to prevent, detect early, and treat ovarian cancer.

This page highlights some of what’s new in the latest research in ovarian cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Prevention of Ovarian Cancer

Women who carry harmful or potentially harmful mutations in the BRCA1 or BRCA2 genes are at increased risk of developing ovarian cancer.  Surgery to remove the ovaries and fallopian tubes in these women is the recommended treatment method and can reduce their lifetime risk of getting ovarian cancer by 95%. However, having this surgery  causes immediate menopause. This may cause health problems if it is much earlier than naturally occurring menopause.

Research has shown that the most common type of ovarian cancer begins in the fallopian tubes , not in the ovaries. This discovery has led doctors to reconsider ways of preventing ovarian cancer.

• Removing fallopian tubes only. An ongoing NCI-sponsored clinical trial is testing whether removing the fallopian tubes but delaying removal of the ovaries will be as effective to reduce the risk of ovarian cancer in women with BRCA1 mutations as removing both the ovaries and fallopian tubes at the same time. This would allow women to maintain premenopausal levels of hormones produced by the ovaries and delay many of the complications associated with menopause.
• Removal of fallopian tubes in people seeking to prevent pregnancy. The discovery that epithelial ovarian cancers most often start in the fallopian tubes has also led to changes in the way some gynecologists approach surgery to prevent pregnancy. Women seeking tubal ligation to prevent pregnancy (often called having your tubes tied) may be offered the option of having their tubes removed instead. Doing so might reduce the possibility of ovarian cancer in the future. 
• Removal of fallopian tubes in people undergoing a hysterectomy. Similarly, some gynecologists recommend that their patients who are undergoing a hysterectomy also have their fallopian tubes removed.
• Testing relatives for gene mutations. NCI is funding efforts to test the relatives of women who have been diagnosed with ovarian cancer in the past.  Researchers are locating women diagnosed with ovarian cancer with the hope to test them and/or their family members for ovarian cancer-related gene mutations. As a result, family members who learn they carry a mutation can take steps to reduce their risk. The overall goal is not only to prevent ovarian cancer, but also to find the best ways to communicate sensitive genetic information to ovarian cancer patients and their family members.

Ovarian Cancer Treatment

Surgery and chemotherapy are the main treatments for ovarian cancer. The location and type of cells where the cancer begins, and whether the cancer is high-grade or low-grade , influences how the cancer is treated. Surgery can cure most people with early-stage ovarian cancer that has not spread beyond the ovaries. For advanced ovarian cancer, the goal of surgery is to remove as much of the cancer as possible, called surgical debulking . 

Platinum-based chemotherapy drugs, such as cisplatin or carboplatin , given in combination with other drugs, such as the targeted therapy bevacizumab (Avastin) , are usually effective in treating epithelial ovarian cancer at any stage. However, in most people with advanced ovarian cancer, the cancer comes back. Treating the cancer again with platinum drugs may work, but eventually the tumors become resistant to these drugs.

Targeted Therapy

Targeted therapy uses drugs or other agents to attack specific types of cancer cells. PARP inhibitors are a type of targeted therapy that can stop a cancer cell from repairing its damaged DNA , causing the cell to die. Cancers in people who have certain mutations in the BRCA genes are considered particularly susceptible to PARP inhibitors. That’s because BRCA genes are involved in the repair of some types of DNA damage, so cancers with BRCA gene alterations already have defects in DNA repair.

The use of PARP inhibitors has transformed treatment for people with advanced epithelial ovarian cancer who have harmful mutations in a BRCA gene. Since the 2014 approval of olaparib (Lynparza) , the first PARP inhibitor to be approved, the number of PARP inhibitors has grown and their uses for people with ovarian cancer have expanded. Now researchers are studying the benefits of combining PARP inhibitors with other drugs.

Clinical trials have shown that using PARP inhibitors as long-term therapy in women with advanced epithelial ovarian cancer delayed progression of the cancer. 

 A different targeted therapy, mirvetuximab soravtansine (Elahere) , is now available to treat women with ovarian cancer that is no longer responding to platinum drugs. FDA recently approved the drug to treat people with platinum-resistant ovarian tumors that produce an excess of a protein called FR-α. Results from a large clinical trial showed that people with this type of ovarian cancer treated with mirvetuximab lived longer overall than people treated with standard chemotherapy .

Treatment after Cancer Progression

Typically, chemotherapy and targeted therapies are stopped once ovarian cancer begins to come back. Clinical trials have shown that where there was more than a 6 month delay between stopping treatment and cancer being found again, resuming the drug bevacizumab (Avastin)  in combination with platinum-based chemotherapy for patients previously treated with bevacizumab  slowed the growth of platinum-sensitive disease . And in women who no longer benefited from platinum-based chemotherapy, non–platinum-based chemotherapy combined with bevacizumab kept the cancer in check longer than chemotherapy alone.

Targeted therapies may also be helpful for people with low-grade ovarian cancer. A trial of the drug trametinib in women with low-grade serous ovarian cancer that had come back showed that it delayed the cancer’s growth compared with treating the cancer with chemotherapy again.

Secondary Surgery

For women with advanced epithelial ovarian cancer that has come back after being in remission, clinical trials have studied the use of secondary surgery or surgery to remove more tumor after the initial surgery with varying results. 

• An NCI-funded phase 3 clinical trial, in patients whose doctor felt that a second surgery could be helpful for treating the cancer, found that secondary surgery followed by chemotherapy did not increase overall survival compared with chemotherapy alone. Of the studies listed, this one reflected the most likely scenario in real-world practice.
• A trial done in China studied a group of patients more likely to benefit from the intervention. The trial tested secondary surgery followed by chemotherapy and did show improvements in how long women with recurrent epithelial ovarian cancer lived without their cancer growing .
• In a third trial, conducted in Europe, researchers identified people with recurrent ovarian cancer who were most likely to benefit from surgery. They found that women who had secondary surgery followed by chemotherapy lived an average of nearly 8 months longer than women who only received chemotherapy.

In the Chinese and European trials, and in an analysis of 64 clinical trials and other studies , the benefits of secondary surgery were observed only in women who had all of their visible cancer removed.

NCI-Supported Research Programs

Many NCI-funded researchers at the National Institutes of Health campus, and across the United States and the world, are seeking ways to address ovarian cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of ovarian cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate this basic information into improving patient outcomes.

The Women’s Malignancies Branch in NCI’s Center for Cancer Research conducts basic and clinical research in breast and gynecologic cancers, including early-phase clinical trials at the NIH Clinical Center in Bethesda, Maryland. 

The Ovarian Specialized Programs of Research Excellence (SPOREs) promote collaborative translational cancer research. This group works to improve prevention and treatment approaches, along with molecular diagnostics , in the clinical setting to help people with ovarian cancer.

The Ovarian Cancer Cohort Consortium , part of the NCI Cohort Consortium, is an international consortium of more than 20 cohort studies that follow people with ovarian cancer to improve understanding of ovarian cancer risk, early detection, tumor differences, and prognosis. 

NCI’s clinical trials programs, the National Clinical Trials Network , Experimental Therapeutics Clinical Trials Network , and NCI Community Oncology Research Program , all conduct or sponsor clinical studies of ovarian cancer.

Clinical Trials for Ovarian Cancer

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for the treatment of ovarian cancer.

Ovarian Cancer Research Results

The following are some of our latest news articles on ovarian cancer research:

Approval of Elahere Expands Treatment Options for Some Advanced Ovarian Cancers

Implanted “Drug Factories” Deliver Cancer Treatment Directly to Tumors

Trametinib Is a New Treatment Option for Rare Form of Ovarian Cancer

When Ovarian Cancer Returns, Surgery May Be a Good Choice for Selected Patients

How Does Ovarian Cancer Form? A New Study Points to MicroRNA

Ovarian Cancer Studies Aim to Reduce Racial Disparities, Improve Outcomes

View the full list of Ovarian Cancer Research Results and Study Updates .

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Ovarian cancer articles from across Nature Portfolio

Ovarian cancer is an abnormal cell growth (tumour) arising in the ovary. The majority of ovarian cancers are epithelial and develop in women over 50. Screening is highly recommended in women with a family history of ovarian cancer.

Latest Research and Reviews

PARP inhibition with rucaparib alone followed by combination with atezolizumab: Phase Ib COUPLET clinical study in advanced gynaecological and triple-negative breast cancers

• Rebecca Kristeleit
• Alexandra Leary
• Linda Mileshkin

3D engineered scaffold for large-scale Vigil immunotherapy production

• Fabienne Kerneis
• Ernest Bognar
• Joerg Lahann

Schlafen 11 further sensitizes BRCA-deficient cells to PARP inhibitors through single-strand DNA gap accumulation behind replication forks

• Hiroshi Onji
• Junko Murai

TP53 somatic evolution in cervical liquid-based cytology and blood from individuals with and without ovarian cancer and BRCA1 or BRCA2 germline mutations

• Talayeh S. Ghezelayagh
• Brendan F. Kohrn
• Rosa Ana Risques

Therapy-induced secretion of spliceosomal components mediates pro-survival crosstalk between ovarian cancer cells

Ovarian cancers frequently develop resistance to therapy. Here, using transcriptomics, proteomics, and preclinical models to analyse paired ascitic fluids before and after chemotherapy in ovarian cancer patients, the authors discover that extracellular secretion and spliceosomal components contribute to therapy resistance, enhancing the DNA damage response in recipient cancer cells.

• Victoria O. Shender
• Ksenia S. Anufrieva
• Vadim M. Govorun

Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1)

• S. Lot Aronson
• Cédric Walker
• Kerstin Hahn

News and Comment

Mirvetuximab soravtansine has activity in platinum-sensitive epithelial ovarian cancer.

• Diana Romero

Mirvetuximab soravtansine superior to chemotherapy in platinum-resistant epithelial ovarian cancer

• Peter Sidaway

A medley of resistance in ovarian cancers

Multi-omic profiling of lesions at autopsy reveals a plethora of resistance mechanisms present within individual patients with ovarian cancer. This highlights the extreme challenge faced in treating end-stage disease and underscores the need for new methods of early detection and intervention.

• Barbara Hernando
• Geoff Macintyre

A biomarker-driven therapy for ovarian cancer

An antibody–drug conjugate showed impressive anti-cancer activity in selected patients with platinum-resistant ovarian cancer, and could become a new standard of care.

• Karen O’Leary

Beating the odds: molecular characteristics of long-term survivors of ovarian cancer

High-grade serous ovarian cancer, the most common form of the disease, is often fatal. This study investigated the genomic and immune characteristics of tumors from women who survived more than 10 years after their initial diagnosis, and compared them with short-term and moderate-term survivors.

Cytoreductive surgery effective after relapse

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Advances in Ovarian Cancer Research: From Biology to Therapeutics

Dear Colleagues,

Recently, substantial progress has been made in treating ovarian cancer, predominantly based on the identification of new molecular targets. For example, PARP inhibitors have been successful largely due to their efficacy in cancers that harbor BRCA mutations or evidence of deficiency in the homologous recombination DNA repair pathway. This collection of articles will address the biological discoveries leading to the next breakthroughs in ovarian cancer research and treatment. Authors are encouraged to submit research studies with translational potential, especially those that include novel biomarkers for treatment effects. This topic thus provides a framework for integrating discoveries at the bench and the bedside.

Dr. Christina M. Annunziata Prof. Dr. Adam R. Karpf Topic Editors

• ovarian cancer
• translational research
• epigenetics
• clinical trials
• tumor biology
• drug discovery

• Immediately share your ideas ahead of publication and establish your research priority;
• Protect your idea from being stolen with this time-stamped preprint article;
• Enhance the exposure and impact of your research;
• Receive feedback from your peers in advance;
• Have it indexed in Web of Science (Preprint Citation Index), Google Scholar, Crossref, SHARE, PrePubMed, Scilit and Europe PMC.

Published Papers (22 papers)

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Ovarian cancer: New treatments and research

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By Nicole Brudos Ferrara

Three cancers — ovarian epithelial cancer, fallopian tube cancer and primary peritoneal cancer — are commonly called ovarian cancer. They arise from the same kind of tissue and are treated similarly.

"The ovaries and fallopian tubes are so anatomically close to each other that we sometimes can't tell if the cancer is coming from the ovary or the fallopian tube," says S. John Weroha, M.D., Ph.D. , a Mayo Clinic oncologist and chair of Mayo Clinic Comprehensive Cancer Center's Gynecologic Cancer Disease Group. "When we diagnose patients with primary peritoneal cancer, I explain that under the microscope, and in the pattern of spread through the body, it looks like ovarian cancer even though the ovaries are not involved."

Primary peritoneal cancer forms in the peritoneum, the tissue that lines the abdominal cavity and the organs within it. Fallopian tube cancer forms in the tissue lining the inside of the tubes that eggs travel through to move from the ovaries to the uterus.

About 85% to 90% of ovarian cancers are ovarian epithelial cancers, also known as epithelial ovarian carcinomas, which form in the tissue lining the outside of the ovaries.

Dr. Weroha says new treatments are helping more people survive ovarian cancer of all types, and researchers are studying new treatments and screening methods in clinical trials. If you've been diagnosed with ovarian cancer, he wants you to know there is hope. Here's why:

New targeted therapies are improving survival.

Surgery and chemotherapy are no longer the only options for ovarian cancer treatment . Targeted therapies use drugs to target and attack cancer cells. These include monoclonal antibodies and poly (ADP-ribose) polymerase, or PARP, inhibitors.

Monoclonal antibodies

Monoclonal antibodies are molecules engineered in the laboratory to find and attach to specific proteins associated with cancer cells. Bevacizumab is a monoclonal antibody used with chemotherapy to treat ovarian cancer recurrence by preventing the growth of new blood vessels that tumors need to grow.

Researchers are combining bevacizumab with new drugs to improve outcomes. One example is a monoclonal antibody recently approved by the Food and Drug Administration (FDA) called mirvetuximab soravtansine for people with ovarian cancer recurrence. This drug is used when a person's cancer was previously treated with at least one systemic therapy to target a protein called folate receptor alpha.

"Ovarian cancers have many folate receptors. Most normal cells don't," says Dr. Weroha. "This drug is an antibody that has chemotherapy stuck onto it. Think of it as a guided missile traveling the body and sticking to cells with folate receptors. In patients whose ovarian cancer has recurred and whose tumors have many folate receptors, mirvetuximab soravtansine can shrink tumors far better than any other therapy. The response rate is about double what you see with any other treatment."

PARP inhibitors

PARP inhibitors are drugs that block DNA repair, which may cause cancer cells to die. Olaparib is an example of a PARP inhibitor used to prevent recurrence in people with ovarian cancer whose tumors have BRCA1 or BRCA2 gene mutations. Research has shown that olaparib can significantly improve survival without recurrence in people with this diagnosis. "This is a front-line treatment, which means this is part of the first treatment regimen patients receive when they are newly diagnosed," says Dr. Weroha.

A vaccine may one day be used to fight ovarian cancer.

Matthew Block, M.D., Ph.D. , a Mayo Clinic medical oncologist, and Keith Knutson, Ph.D. , a Mayo Clinic researcher, are developing a vaccine to prevent ovarian cancer tumors from returning in people with advanced ovarian cancer whose tumors have recurred after surgery and chemotherapy.

White blood cells are extracted from a blood draw and manufactured to become dendritic cells — immune cells that boost immune responses. These cells are returned to the patient in vaccine form to trigger the immune system to recognize and fight the cancer.

The vaccine will be given in combination with an immunotherapy drug called pembrolizumab to identify and kill any tumors that don't respond to the dendritic cells.

"Pembrolizumab is in a category of drugs called immune checkpoint inhibitors ," says Dr. Weroha. "This drug is designed to release the brakes on the immune system to allow it to do what it naturally wants: kill things it doesn't like. The hope is that the vaccine combined with the immunotherapy drug will kill a lot of ovarian cancer. It's exciting research."

A screening test may be on the horizon.

There is no screening test for ovarian cancer, but Jamie Bakkum-Gamez, M.D. , a Mayo Clinic gynecologic oncologist, is hoping to change that. She and her research team discovered that methylated DNA markers could be used to identify endometrial cancer through vaginal fluid collected with a tampon. Eventually, this same science could extend to ovarian cancer.

Methylation is a mechanism cells use to control gene expression — the process by which a gene is switched on in a cell to make RNA and proteins. When a certain area of a gene's DNA is methylated, the gene is turned off or silenced, indicating that a gene is a tumor suppressor. The silencing of tumor suppressor genes is often an early step in cancer development and can suggest cancer.

Dr. Bakkum-Gamez and her colleagues developed a panel of methylated DNA markers that could distinguish between endometrial cancer and noncancerous tissue in vaginal fluid. Based on this research, she hopes to develop an affordable tampon-based home screening test for endometrial, ovarian and cervical cancers, as well as high-risk HPV .

"This is exciting because this type of screening test can be used by people living in rural areas,” says Dr. Weroha. “If it's successful, it could help healthcare professionals identify ovarian and other gynecologic cancers sooner, when they're more treatable, in people living in all the communities we serve.”

A gynecologic oncologist and clinical trials can help you get the best possible treatment.

If you've been diagnosed with ovarian cancer, Dr. Weroha recommends making an appointment with a gynecologic oncologist . "A gynecologic oncologist will be up to date on the current treatment recommendations and the management of side effects. That's important," he says. "Once the plan is set, however, any medical oncologist could implement it.”

Dr. Weroha also recommends newly diagnosed patients ask their care teams if they are candidates for PARP inhibitors, mirvetuximab or clinical trials. "PARP inhibitors and mirvetuximab are newer treatments that could influence the outcome of your overall treatment. Always ask about clinical trials because when ovarian cancer recurs, there is no treatment so good that we can stop looking for something better," he says. "There is a very realistic hope that if your cancer were to come back, we would have something better that we don't have today."

Learn more about ovarian cancer and find a clinical trial at Mayo Clinic.

Join the Gynecologic Cancers Support Group on Mayo Clinic Connect , an online community moderated by Mayo Clinic for patients and caregivers.

Join the next virtual Gynecologic Cancer Support Meeting: Women of S-Teal . Monthly meetings are held every second Monday from 5:30 to 6:30 p.m. ET.

Also, read these articles:

• A step toward detecting endometrial cancer earlier
• Harnessing the immune system to fight ovarian cancer
• Life after ovarian cancer: Coping with side effects, fear of recurrence, and finding support
• New surgical method for ovarian cancer lights up lesions
• Is a cancer clinical trial right for me?
• New chemotherapy approach for late-stage cancers

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Ovarian Cancer Research Highlights

Ovarian cancer causes more deaths in women living in the United States than any other cancer of the female reproductive system. The American Cancer Society’s (ACS) research programs help find answers to critical questions:

• How can ovarian cancer be diagnosed early?
• How can the risk of developing ovarian cancer be lowered?
• Are there more effective treatments?
• What could help survivors have a better quality of life?

We continue to fund research to help save more lives in the future.  

Ovarian Cancer Still Causes the Most Deaths from Gynecological Cancer

About 90% of cases are epithelial ovarian cancer, and most of those cases are high-grade serous tumors, which have the fewest established risk factors and the worst prognosis.

Risk & Prevention Studies

We've learned more about the risk of developing ovarian cancer.

Thanks to CPS-II and CPS-3 participants!   

The ACS’s CPS-II Nutrition Cohort is part of the Collaborative Group on Epidemiological Studies of Ovarian Cancer. This group helped establish the increased risk for ovarian cancer in women with excess body weight and the decreased risk of ovarian cancer for women who use oral contraceptives.”

Alpa Patel, PhD

Senior Vice President Population Science

American Cancer Society

Ovarian Cancer Statistics on Age

It's rare for women younger than 40 to have ovarian cancer.

Half of all ovarian cancers are found in women age 63 or older.

Featured Term: Biomarker

A measurable molecular, genetic, chemical, or physical characteristic in the blood or other bodily fluids, such as sweat and tears, that is a sign of a normal or abnormal process or of a health condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease. 

Featured Term: Susceptibility Biomarkers

A biomarker that signals the potential, or risk, a person has to develop a disease before they have symptoms. For instance, low-density lipoprotein (LDL) cholesterol is a susceptibility biomarker for heart disease.

Early Detection Studies

Glowing “fingerprint” from a blood test may find ovarian cancer early.

Machine learning and tiny glowing nanosensors enable the detection of ovarian cancer from a blood test.  

Ovarian Cancer May Start in Fallopian Tube Cells

By studying fallopian tube cells from cancer-free women, researchers learned more about the origin of the most deadly type of ovarian cancer.

A New Gene Is Linked with the Deadliest Type of Ovarian Cancer

Researchers develop a new genetically engineered mouse ovarian cancer model to explore potential new drug targets to treat epithelial ovarian cancer.

Ovarian Cancer Statistics on Racial Disparities

the rank Black people have on a 1-to-5 scale (with 5 as the lowest) for the incidence rate of ovarian cancer based on race and ethnicity

the rank Black people have on a 1-to-5 scale (with 5 as the lowest) for the death rate of ovarian cancer based on race and ethnicity

the rank American Indian and Alaska Native people have on a 1-to-5 scale (with 5 as the lowest) for incidence rate AND death rate for ovarian cancer based on race and ethnicity

Treatment Studies

New gene-testing tools may personalize ovarian cancer care.

Researchers say using next-generation sequencing technology as a diagnostic tool may increase precision treatment plans for people with ovarian cancer.

Chromosome-Hoarding Ovarian Cancer Cells May Help Treatment

Using new CRISPR tools, researchers learn extra chromosomes promote tumor growth and paradoxically may help activate some treatments.

Testing Nanoparticles to Deliver Drugs to Mice with Ovarian Cancer

Researchers find that drugs successfully attack metastasized ovarian tumors when they're given via teeny nanoparticles injected directly into the abdomen.

Ovarian Cancer Advocacy

Listen to Vanessa's story: She's an ovarian cancer survivor and now advocates to help other survivors have access to care.

ACS Ovarian Cancer Research News

Sitting Too Much Increases Cancer Risk in Women

Statistics (Downloadable PDFs)

Cancer Facts & Figures 2024

Special Section Ovarian Cancer

Useful Links

Ovarian Cancer - ACS Cancer Statistics Center

Glossary for Nonscientists

We Fund Ovarian Cancer Researchers Across the US

The ACS funds scientists who conduct research about ovarian cancer at medical schools, universities, research institutes, and hospitals throughout the United States. We use a rigorous and independent  peer review process  to select the most innovative research projects proposals to fund. 

These grant statistics are as of August 1, 2023.

ovarian cancer research grants

funding for ovarian cancer research

Help us end cancer as we know it, for everyone.

If this was helpful, donate to help fund patient support services, research, and cancer content updates.

Ovarian Cancers: Evolving Paradigms in Research and Care (2016)

Chapter: 1 introduction and background.

Introduction and Background

Although recent years have seen many promising advances in cancer research, there remain surprising gaps in the fundamental knowledge about and understanding of ovarian cancer. Researchers now know that ovarian cancer, like many other types of cancer, should not be thought of as a single disease; instead, several distinct subtypes exist with different origins, different risk factors, different genetic mutations, different biological behaviors, and different prognoses, and much remains to be learned about them. For example, researchers do not have definitive knowledge of exactly where these various ovarian cancers originate and how they develop. Such unanswered questions have impeded progress in the prevention, early detection, treatment, and management of ovarian cancers. In particular, the failure to achieve major reductions in ovarian cancer morbidity and mortality during the past several decades is likely due to several factors, including

• A lack of research focusing on specific disease subtypes;
• An incomplete understanding of genetic and nongenetic risk factors;
• An inability to develop and validate effective screening and early detection tools;
• Inconsistency in the delivery of the standard of care;
• Limited evidence-based personalized medicine approaches tailored to the disease subtypes and other tumor characteristics; and
• Limited attention paid to research on survivorship issues, including supportive care with long-term management of active disease.

The symptoms of ovarian cancers can be nonspecific and are often not seen as indicating a serious illness by women or their health care providers until the symptoms worsen, at which point the cancer may be widespread and difficult to cure. The fact that these cancers are not diagnosed in many women until they are at an advanced stage is a major factor contributing to the high mortality rate for ovarian cancer, especially for women with high-grade serous carcinoma (HGSC)—the most common and lethal subtype. Indeed, roughly two-thirds of women with ovarian cancer are diagnosed with an advanced-stage cancer or with a cancer that has not been definitively staged, and the 5-year survival rate for these women is less than 30 percent (Howlader et al., 2015). Although many ovarian cancers respond well to initial treatment, including the surgical removal of grossly visible tumor (cytoreduction) and chemotherapy, the vast majority of the tumors recur. Recurrent ovarian cancers may again respond to further treatment, but virtually all of them will ultimately become resistant to current drug therapies.

Finally, less emphasis has been placed on research that focuses on how to improve therapeutic interventions by subtype or on how to reduce the morbidity of ovarian cancers. Little emphasis has been placed on understanding survivorship issues and the supportive care needs of women with ovarian cancer, including management of the physical side effects of treatment (including both initial and chronic, ongoing therapies) and addressing the psychosocial effects of diagnosis and treatment. The lasting impact of a diagnosis of ovarian cancer and its related treatment can be significant both for the women who experience recurrent disease and for the women who experience long (or indefinite) periods of remission. This report gives an overview of the state of the science in ovarian cancer research, highlights the major gaps in knowledge in that field, and provides recommendations that might help reduce the incidence of and morbidity and mortality from ovarian cancers by focusing on promising research themes and technologies that could advance risk prediction, early detection, comprehensive care, and cure.

STUDY CHARGE AND APPROACH

In spite of their high mortality rates, ovarian cancers often do not receive as much attention as other cancers. In part, this is because ovarian cancers are relatively uncommon. Furthermore, ovarian cancer has been called a “silent killer” because researchers once believed that there were no perceptible symptoms in the earlier stages of the disease (Goff, 2012). However, more recent research has shown that most women diagnosed with ovarian cancer report symptoms such as bloating, pelvic or abdominal pain, and urinary symptoms, and many women recall having these symptoms

for an extended period of time before diagnosis (Goff et al., 2000, 2004). Often, due to the nonspecific nature of ovarian cancer symptoms, patients and physicians do not recognize these early symptoms as indicative of ovarian cancer (Gajjar et al., 2012; Jones et al., 2010; Lockwood-Rayermann et al., 2009).

In this context, in 2006 the U.S. Congress passed the Gynecologic Cancer Education and Awareness Act of 2005, 1 which amended the Public Health Service Act (42 U.S.C. 247b-17) to direct the secretary of the U.S. Department of Health and Human Services to launch a campaign to “increase the awareness and knowledge of health care providers and women with respect to gynecologic cancers.” The law is commonly known as Johanna’s Law in memory of Johanna Silver Gordon, a public school teacher from Michigan who died from late-stage ovarian cancer (Twombly, 2007). The law was reauthorized in 2010, 2 and, as part of the Consolidated Appropriations Act of 2014, Congress directed the Centers for Disease Control and Prevention (CDC) to use funds from Johanna’s Law to perform a review of the state of the science in ovarian cancer. 3

Study Charge

In the fall of 2014, with support from the CDC, the Institute of Medicine (IOM) formed the Committee on the State of the Science in Ovarian Cancer Research to examine and summarize the state of the science in ovarian cancer research, to identify key gaps in the evidence base and challenges to addressing those gaps, and to consider opportunities for advancing ovarian cancer research (see Box 1-1 ). The committee determined that the best way to facilitate progress in reducing morbidity and mortality would be to identify the research gaps that were most salient and that, if addressed, could affect the greatest number of women.

The committee was also asked to consider ways to translate and disseminate new findings and to communicate these findings to all stakeholders. This report, therefore, not only describes evidence-based approaches to translation and dissemination, but it also suggests strategies for communicating those approaches.

________________

1 Gynecologic Cancer Education and Awareness Act of 2005, Public Law 475, 109th Cong., 2nd sess. (January 12, 2007).

2 To reauthorize and enhance Johanna’s Law to increase public awareness and knowledge with respect to gynecologic cancers, Public Law 324, 111th Cong., 2nd sess. (December 22, 2010).

3 Explanatory statement submitted by Mr. Rogers of Kentucky, Chairman of the House Committee on Appropriations regarding the House amendment to the Senate amendment on H.R. 3547, consolidated... , 113th Cong., 2nd sess., Congressional Record 160, no. 9, daily ed. (January 15, 2014):H 1035.

BOX 1-1 Statement of Task

An ad hoc committee under the auspices of the Institute of Medicine will review the state of the science in ovarian cancer research and formulate recommendations for action to advance the field. The committee will:

• Summarize and examine the state of the science in ovarian cancer research;
• Identify key gaps in the evidence base and the challenges to addressing those gaps;
• Consider opportunities for advancing ovarian cancer research; and
• Examine avenues for translation and dissemination of new findings and communication of new information to patients and others.

The committee will make recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of and morbidity and mortality from ovarian cancer.

The committee emphasizes that its charge was to focus on research in ovarian cancer and, particularly, to focus on the gaps in the evidence base that, if addressed, would have the greatest impact on the lives of women diagnosed with or at risk for ovarian cancer. The committee did not explore issues affecting the care of women with ovarian cancer (e.g., health insurance coverage and policy issues) in depth. For example, while the regulatory process for drug approval is interconnected with the clinical trial enterprise (e.g., the design of clinical trials may determine what data are gathered and, in turn, affect the approval process), a full examination of issues related to the approval of new drugs was beyond the scope of this report. Furthermore, it was outside the scope of this report to fully evaluate specific research programs in ovarian cancer. In addition, this report does not offer an exhaustive cataloguing of every actor engaged in ovarian cancer research, nor does it detail every effort made by stakeholders to engage in dissemination and implementation efforts. Rather, the examples given in this report are meant to highlight the efforts being made, recognizing there are many other similar efforts.

Finally, the committee focused as much as possible on the research gaps and the challenges to addressing those gaps that are unique to ovarian cancer. However, those research gaps and challenges that are common to all types of cancer research, or even to all health care research, are described as appropriate. For example, while the clinical trials system is extremely important to the ovarian cancer research enterprise, many of the outstanding

questions and concerns related to the clinical trials system are shared with all types of cancer research and could not be explored or discussed in detail. Therefore, the committee turned to previous IOM reports specific to the clinical trials system in general for guidance, and then considered aspects of the system that are particularly relevant for ovarian cancer research.

Study Approach

The study committee included 15 members with expertise in ovarian cancer, gynecologic oncology, gynecologic pathology, gynecologic surgery, molecular biology, cancer genetics and genomics, genetic counseling, cancer epidemiology, immunology, biostatistics, bioethics, advocacy, survivorship, and health communication. (See Appendix E for biographies of the committee members.)

A variety of sources informed the committee’s work. The committee met in person four times, and during two of those meetings it held public sessions to obtain input from a broad range of relevant stakeholders. In addition, the committee conducted extensive literature reviews, reached out to a variety of public and private stakeholders, and commissioned one paper.

The committee encountered a number of challenges. In some cases, it found itself limited by what was available in the published literature. At other times, it was challenged by the use of different methodologies for the classification of ovarian cancers in the research literature. For instance, many studies in the literature consolidate all types of ovarian cancer instead of studying and reporting them by subtype. In its review of the evidence, the committee discerns, where possible, whether the reported findings apply to ovarian cancers as a whole or to particular subtypes. One other major challenge to reviewing and summarizing the evidence base on ovarian cancer, particularly in summarizing the epidemiology by subtype, was the way that the grading, classification, and nomenclature for ovarian cancers have varied over the years.

In order to guide its deliberative process, the committee chose to make recommendations about research gaps based on the continuum of cancer care (see Figure 1-1 ). The committee focused on cross-cutting research areas critical to each phase of the continuum: the basic biology of ovarian cancers, innovative clinical trial design, intervention development, methods to reduce practice-related disparities, and supportive care research and practice. Finally, the committee considered evidence and strategies for the dissemination and implementation of knowledge across all of these domains.

DEFINITIONS OF KEY TERMS

This section provides definitions of several key terms that are relevant to this report, and also provides an explanation of how the committee

FIGURE 1-1 Framework for research in ovarian cancer. NOTE: Colored figures represent phases of the ovarian cancer care continuum where research can be focused. Black boxes indicate critical areas of ongoing cross-cutting research that span these phases.

selected terms for consistency throughout the report. A glossary including more terms is provided in Appendix B , and a list of key acronyms is included in Appendix A .

Target Population

This report is concerned with women with ovarian cancers. However, the committee recognizes that there is a small subpopulation of transgender men who may be at risk for ovarian cancers, particularly due to the use of testosterone therapy (Dizon et al., 2006; Hage et al., 2000).

Basic Cancer Terminology

The terms “cancer,” “carcinoma,” and “tumor” can be confused or interchanged at times. Cancer is “a term for diseases in which abnormal cells divide without control and can invade nearby tissues,” while a tumor (which can be cancerous or noncancerous) is “an abnormal mass of tissue that results when cells divide more than they should or do not die when they should” (NCI, 2015d). Carcinomas are cancers that “begin in the skin or in tissues that line or cover internal organs” (i.e., arising from epithelial cells) (NCI, 2015d). As was noted previously, this report focuses on ovarian carcinomas, because they are the most common and most lethal of the ovarian cancer subtypes.

While the committee endeavored to focus on carcinomas wherever possible, there were times when that was not possible, and the terms “cancer” and “tumor” are used when appropriate. For example, many studies are based on ovarian cancers collectively and do not analyze data based on the subtypes. The committee also uses the term “tumor” when discussing the physical mass itself. Finally, although the term “ovarian cancer” technically represents an array of disease subtypes, the committee refers to the disease in the plural form (i.e., “ovarian cancers”) whenever appropriate in order to emphasize the heterogeneity of the disease and all its subtypes.

When ovarian cancer reappears in a woman, it is usually referred to as “relapsed” or “recurrent” disease. The National Cancer Institute (NCI) defines cancer recurrence as “cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body” (NCI, 2015d). Noting that a cancer that has recurred is also called “relapsed cancer,” the NCI defines relapse as “the return of a disease or the signs and symptoms of a disease after a period of improvement.” In this report, for consistency the committee uses only the terms “recurrent” or “recurrence”—and not “relapsed” or “relapse”—but

it recognizes that there may be subtle differences, preferences, or interpretations in the use of the two terms.

DEFINING AND CLASSIFYING OVARIAN CANCERS

“Ovarian cancer” is a generic term that can be used for any cancer involving the ovaries. The ovaries are composed of several different cell types, including the germ cells, specialized gonadal stromal cells (e.g., granulosa cells, theca cells, Leydig cells, and fibroblasts), and epithelial cells; ovarian cancers can arise from any of these cell types. Ovarian cancers with epithelial differentiation (carcinomas) account for more than 85 percent of ovarian cancers and are responsible for most ovarian cancer–related deaths (Berek and Bast, 2003; Braicu et al., 2011; SEER Program, 2015; Seidman et al., 2004). Consequently, this report will focus on the biology of ovarian carcinomas, while recognizing that although other, less common types of ovarian malignancies do exist, they are responsible for a smaller fraction of ovarian cancer–related deaths.

As with ovarian cancers in general, ovarian carcinomas are quite heterogeneous and come in a variety of different tumor types (see Figure 1-2 ). The major ovarian carcinoma subtypes are named according to how closely the tumor cells resemble normal cells lining different organs in the female genitourinary tract. Specifically, serous, endometrioid, and a subset

FIGURE 1-2 Percentage of cases by major ovarian carcinoma subtype. NOTE: Other* refers to mixed or transitional carcinomas where it is not possible to categorize to a single subtype. SOURCE: Gilks et al., 2008; Seidman et al., 2003, 2004.

of mucinous carcinomas exhibit morphological features that are similar to normal epithelial cells in the fallopian tube, endometrium, and endocervix, respectively. Furthermore, clear cell carcinomas resemble cells seen in the gestational endometrium (Scully et al., 1999).

Over the past several years, researchers have developed a streamlined classification scheme in which the majority of ovarian carcinomas can be divided into five types:

• Endometrioid carcinoma (EC),
• Clear cell carcinoma (CCC),
• Low-grade serous carcinoma (LGSC), and
• Mucinous carcinoma (MC) (Gurung et al., 2013; Kalloger et al., 2011).

Some researchers have offered an even simpler classification with a scheme in which ovarian carcinomas are divided into Type I and Type II tumors based on shared features (Shih and Kurman, 2004). In this scheme, Type I carcinomas are low-grade, relatively unaggressive, and genetically stable tumors that often arise from recognizable precursor lesions such as endometriosis or benign tumors and frequently harbor somatic mutations that deregulate specific cell signaling pathways or chromatin remodeling complexes. ECs, CCCs, MCs, and LGSCs are considered Type I tumors and are often characterized by KRAS, BRAF , or PTEN mutations. Type II carcinomas are high-grade, biologically aggressive tumors from their inception, with a propensity for metastasis from small, even microscopic, primary lesions. HGSCs represent the majority of Type II tumors and are characterized by the mutation of TP53 and frequent mutations of genes (e.g., BRCA1 and BRCA2 ) that lead to homologous recombination defects (Pennington et al., 2014).

Because the data collected thus far provide compelling evidence that each of the various Type I tumors has distinct biological and molecular features, these tumors will be referred to by their specific histologic type throughout the remainder of this report. However, the Type I and Type II terminology will be used where necessary, most often in referring to studies conducted using this classification scheme. Furthermore, because the majority of ovarian carcinomas are HGSCs, and HGSCs are the subtype with the worst prognosis, this report will primarily focus on this subtype. When referring to historical or large-scale epidemiologic studies of ovarian cancer for which the tumor subtypes were not specified, readers can reasonably assume that most of the tumors were HGSCs.

After being classified by subtype, tumors are usually also assigned a grade, based on how closely the tumor cells resemble their normal counter-

parts. Both two-grade and three-grade systems have been applied in various situations; in both types of systems, the lower-grade tumors more closely resemble normal cells than the higher-grade tumors (Malpica et al., 2004; Silverberg, 2000).

OVARIAN CANCER PATTERNS AND DEMOGRAPHICS 4

Although ovarian cancer is relatively rare, it is one of the deadliest cancers. It was estimated that more than 21,000 women in the United States would receive a diagnosis of an ovarian cancer in the year 2015 5 (Howlader et al., 2015). This represents almost 12 new cases for every 100,000 women and 2.6 percent of all new cancer cases in women in the United States. Nearly 200,000 women in the United States are living with ovarian cancer in any given year, and approximately 1.3 percent of all American women will be diagnosed with ovarian cancer at some point in their lives, which qualifies ovarian cancer as a rare disease as defined by the National Institutes of Health (NIH) Genetic and Rare Diseases Information Center (NIH, 2015a). Still, according to estimates, more than 14,000 American women will have died from ovarian cancer in 2015, which corresponds to approximately 7.7 deaths per 100,000 women and 5.1 percent of all cancer deaths among American women (ACS, 2015; Howlader et al., 2015). Despite its relatively low incidence, ovarian cancer is the fifth leading cause of cancer deaths among U.S. women and the eighth leading cause of women’s cancer deaths worldwide (Ferlay et al., 2015; Howlader et al., 2015). By comparison, breast cancer is more common—among American women the estimated number of new cases of breast cancer each year is 10 times the number of new cases of ovarian cancer—but ovarian cancer is more deadly, with a death-to-incidence ratio that is more than three times higher than for breast cancer (Howlader et al., 2015) (see Figure 1-3 ).

The survival rate for ovarian cancer is quite low. For 2005 to 2011, the 5-year survival rate in the United States was just 45.6 percent. By contrast, the 5-year survival rate in the United States for the same period was nearly 90 percent for breast cancer, more than 80 percent for endometrial cancer, and nearly 70 percent for cervical cancer. However, given the typical course of initial remission and subsequent recurrence for women with ovarian cancer, the 5-year survival metric may not reflect the overall disease course. At advanced stages, MCs and CCCs in particular have poorer prognoses and survival rates than other carcinoma subtypes (Mackay et al., 2010).

4 Terminology to describe race and ethnicity reflects the terminology used in the original sources.

5 Because historical epidemiologic data typically combine the multiple types of ovarian cancer, they are discussed as a single disease in this discussion of epidemiology.

FIGURE 1-3 The ratio between the death and incidence rates for ovarian, breast, endometrial, and cervical cancers per 100,000 women in the United States, 2008–2012. SOURCE: Howlader et al., 2015.

The incidence of ovarian cancer has declined slightly since the mid-1970s, when the incidence was approximately 16 new cases per 100,000 women (Howlader et al., 2015). Mortality from ovarian cancer has also declined—from 9.8 deaths per 100,000 women in 1975 to 7.4 deaths per 100,000 women in 2012. However, the decline in mortality is relatively small when compared to reductions in death rates achieved for most other female gynecological cancers and for breast cancer in women. For example, the death rate from breast cancer fell by one-third between 1975 and 2012, from 31.4 deaths per 100,000 women to 21.3 deaths per 100,000, and the death rate from cervical cancer dropped by more than half during that same period, from 5.6 deaths per 100,000 women to 2.3 deaths per 100,000.

Among women who were diagnosed with ovarian cancer between 1975 and 1977, only 36 percent lived 5 years or more, while nearly half (46 percent) of women diagnosed with ovarian cancer between 2005 and 2007 lived at least 5 years beyond their diagnosis (Howlader et al., 2015). However, that improvement in survival rates was driven primarily by improvements in survival among white women; survival rates decreased (from 42 to 36 percent) over the same period for black women (ACS, 2015; also see section Race and Ethnicity later in this chapter).

Stage Distribution

Ovarian cancer’s high mortality and low survival rates can be attributed in part to the fact that it is rarely diagnosed at an early stage. Indeed, 60 percent of women are diagnosed with advanced disease, when the cancer has already spread beyond the ovary to distant organs or lymph nodes (Howlader et al., 2015). In comparison, as seen in Figure 1-4 , other female cancers are more commonly diagnosed during the localized or regional stages.

The relatively late stage of diagnosis for ovarian cancer is particularly important because survival is highly correlated with the stage at diagnosis (see Figure 1-5 ). While the 5-year survival rate is 45.6 percent overall, it is substantially higher for women diagnosed while the cancer is still at the localized stage (92.1 percent) or the regional stage (73.2 percent), and it is substantially lower for women diagnosed at the distant stage (28.3 percent) (ACS, 2015; Howlader et al., 2015). Survival is lowest among women who receive an unstaged ovarian cancer diagnosis (22.9 percent).

White and black women show similar patterns of stage distribution (see Figure 1-6 ). However, there is a difference in stage of diagnosis in women

FIGURE 1-4 Distribution (percentage) of stage of diagnosis for cancers of the breast, endometrium, cervix, and ovary among U.S. women, 2005–2011. SOURCE: Howlader et al., 2015.

FIGURE 1-5 Five-year relative survival (percentage) from ovarian cancer by stage at diagnosis among U.S. women, 2005–2011. SOURCE: Howlader et al., 2015.

FIGURE 1-6 Stage distribution (percentage of cases) at diagnosis among white and black U.S. women diagnosed with ovarian cancer, 2003–2009. SOURCE: Howlader et al., 2015.

of different ages, with women younger than age 65 tending to be diagnosed at earlier stages than women older than age 65 (see Figure 1-7 ).

Ovarian cancer incidence increases with age, with a sharp increase in the rate beginning in the mid-40s (see Figure 1-8 ). From 2008 to 2012, nearly 88 percent of all new cases of ovarian cancer occurred among women ages 45 and older, with 69 percent of cases among women ages 55 and older, and the average age at diagnosis was 63 years. A half-century ago, most cases occurred among women between the ages of 35 and 63, and the average age at diagnosis was 48.5 years (Munnell, 1952).While the age-adjusted incidence rate for ovarian cancer among all women is nearly 12 cases per 100,000 women, the rate varies sharply with age, with women younger than age 65 having an incidence rate of 7.5 cases per 100,000 women while women 65 years old and older have an incidence rate of more than 42 cases per 100,000 women (Howlader et al., 2015).

Mortality rates also increase sharply with age. The death rate for women aged 65 and older is approximately 13 times that of women less than age 65 (see Figure 1-9 ). Furthermore, while mortality rates have de-

FIGURE 1-7 Stage distribution (percentage of cases) at diagnosis among women diagnosed with ovarian cancer by age, 2003–2009. SOURCE: Howlader et al., 2015.

FIGURE 1-8 Age-adjusted incidence of ovarian cancer per 100,000 women in the United States by age group. SOURCE: SEER Program, 2015.

FIGURE 1-9 Trends in age-adjusted death rates from ovarian cancer per 100,000 women in the United States by age group, 1975–2012. SOURCE: Howlader et al., 2015.

clined overall in the past 40 years, most of this decline is attributable to decreases in mortality among women diagnosed with ovarian cancer less than age 65 (ACS, 2015; Howlader et al., 2015).

Race and Ethnicity

The patterns of ovarian cancer incidence and mortality differ substantially among women of different races and ethnic backgrounds (see Figure 1-10 ). Whites have the highest incidence of ovarian cancer, followed by Hispanics, American Indian/Alaska Natives, blacks, and Asian/Pacific Islanders (ACS, 2015; Howlader et al., 2015; Singh et al., 2014). The 5-year survival rate is highest among Asian/Pacific Islanders, followed by Hispanics, whites, American Indian/Alaska Natives, and blacks, while mortality rates are highest among whites, followed by blacks, Hispanics, American Indian/Alaska Natives, and Asian/Pacific Islanders. A particularly dramatic contrast can be seen between black and Asian/Pacific Islander women. While the two groups are similar in having low incidence rates, black women have the second-highest mortality rates and the lowest survival rates, while Asian/Pacific Islanders have the lowest mortality and the highest survival rates. The incidence of ovarian cancer, particularly HGSC, is higher than average in women of Ashkenazi Jewish ancestry, in part because of the higher prevalence of deleterious mutations in cancer-predisposition genes such as BRCA1 and BRCA2 among these women (ACS, 2015; Moslehi et al., 2000).

FIGURE 1-10 Age-adjusted ovarian cancer incidence and mortality per 100,000 U.S. women by race and ethnicity, 2008–2012. SOURCE: Howlader et al., 2015.

Furthermore, the variations in the incidence rates of ovarian cancer by race and ethnicity change as women age (see Figure 1-11 ). For example, whites and Asian/Pacific Islanders have similar incidence rates until around age 50, when their incidence rates begin to diverge. White women aged 45–49 have an age-specific incidence rate of 15.1 cases per 100,000, and Asian/Pacific Islanders of the same age group have a very similar rate of 15.5 cases per 100,000. By contrast, white women aged 80–84 have an incidence rate of 50.8 cases per 100,000, while Asian/Pacific Islanders of the same age group have a dramatically lower rate of 30.1 cases per 100,000.

Historical trends also show considerable variations by race. Between 2003 and 2012, mortality rates decreased significantly among whites and Hispanics, while declines in mortality among blacks, Asian/Pacific Island-

FIGURE 1-11 Age-specific incidence rates of ovarian cancer per 100,000 women in the United States by race/ethnicity and age at diagnosis, 2008–2012. NOTE: Rates for American Indian/Alaska Natives are only displayed for ages 50 through age 69, because the number of cases in other age groups were less than 16 per age group. SOURCE: SEER Program, 2015.

ers, and American Indian/Alaskan Natives were not statistically significant (Howlader et al., 2015). Moreover, while survival rates have increased among women overall and among white women since the mid-1970s, survival rates have declined slightly among black women (see Figure 1-12 ). Furthermore, although black women had higher rates of survival compared to white women and to women overall in 1975, by the mid-1980s survival rates had begun to reverse, such that black women now have lower survival rates than white women and women of all races overall even despite gains in survival among blacks in the 1990s (ACS, 2015).

In the United States, there are slight geographic variations in ovarian cancer incidence, but these variations are not significant (Howlader et al., 2015; Ries et al., 2007). However, the differences in mortality from state to state are significant. In the United States, from 2008 to 2012 the death rate for ovarian cancer was 7.7 deaths per 100,000 women. During that same period, the age-adjusted death rates by state ranged from a low of 5.3 deaths per 100,000 women in Hawaii to a high of 9.0 deaths per 100,000 women in Oregon (Howlader et al., 2015). Despite the wide variation

FIGURE 1-12 Trends in 5-year relative survival rates (percentage) for ovarian cancer among U.S. women by race, 1975–2011. SOURCE: Howlader et al., 2015.

across the states, only Alabama, Oregon, Pennsylvania, and Washington have significantly higher rates, statistically speaking, than the United States as a whole, while only Florida, Hawaii, and Texas have significantly lower rates than the national average.

Ovarian cancer incidence and mortality also vary internationally, with incidence and mortality rates being higher in more developed regions than in less developed regions (Ferlay et al., 2015).

Aside from genetics (e.g., the higher proportion of mutations in cancer-predisposition genes among Ashkenazi Jewish women), the reasons behind the racial and ethnic differences in outcomes are unknown, but they might be explained in part by other variables such as differences in access to health care or the quality of that care (Baicker et al., 2005; IOM, 2003, 2012). Similarly, the reasons behind geographic variation in the demographics of ovarian cancer are unknown, and might be explained by other variables such as race and ethnicity (e.g., the higher proportion of Asian and Pacific Islanders in Hawaii) or differences in access to health care or the quality of that care in different geographic regions (Baicker et al., 2005; IOM, 2003, 2012). (See Chapter 4 for more on access and standards of care for women with ovarian cancer.) Overall, as noted previously, reporting on the demographics and epidemiology of ovarian cancer is challenging because of the fact that most of the data sources aggregate the various subtypes, and even when the data are reported by subtype, differences in the grading, classification, and nomenclature of the subtypes create challenges in summarizing and comparing data.

THE LANDSCAPE OF STAKEHOLDERS IN OVARIAN CANCER RESEARCH

Many public and private organizations are involved in funding, supporting, and carrying out ovarian cancer research, and they are involved in a variety of ways. The research is sometimes focused on ovarian cancers exclusively, but it sometimes looks at broader populations (e.g., women with gynecologic cancers). A complete cataloguing of every stakeholder in ovarian cancer research and of their individual efforts is beyond the scope of this report. Instead, this section offers an overview of the wide range of stakeholders and highlights the areas of ovarian cancer research that are getting the most attention and the methods used by stakeholders to communicate about new findings in ovarian cancer research.

Federal Stakeholders

While there are a number of different federal stakeholders in ovarian cancer research, the CDC, the U.S. Department of Defense (DoD), and the NIH (and the NCI in particular) are collectively responsible for the majority of the funding for ovarian cancer research at the federal level. The sections below give an overview of the funding levels and focus areas for these agencies. Where possible, the areas of focus are presented in alignment with the Common Scientific Outline (CSO), an international classification system used by cancer researchers to compare research portfolios. The CSO consists of seven broad areas of interest:

• Etiology (causes of cancer);
• Prevention;
• Early detection, diagnosis, and prognosis;
• Cancer control, survivorship, and outcomes research; and
• Scientific model systems (DoD, 2015b).

Centers for Disease Control and Prevention

The CDC conducts and supports studies, often in collaboration with partners, to “develop, implement, evaluate, and promote effective cancer prevention and control practices” (CDC, 2015). In general, the CDC approaches cancer by monitoring cancer demographics (surveillance), by conducting research and evaluation, by partnering with other stakeholders to help translate evidence, and by developing educational materials (CDC, 2015). Most of the CDC’s work in ovarian cancer is performed through its Division of Cancer Prevention and Control. 6 Since fiscal year (FY) 2000, the CDC has received about $5 million annually in congressional appropriations to support its Ovarian Cancer Control Initiative. In addition, in 2008 the CDC started receiving funds under Johanna’s Law to improve communication with women regarding gynecologic cancers. The CDC’s Inside Knowledge 7 campaign works to raise awareness about cervical, ovarian, uterine, vaginal, and vulvar cancers. Between 2010 and 2014, ads produced for the Inside Knowledge campaign were seen or heard around 3.5 million times and were worth a total of $136 million in donated ad value (CDC, 2014).

6 For more information, see http://www.cdc.gov/cancer/dcpc/about (accessed July 21, 2015).

7 For more information, see http://www.cdc.gov/cancer/knowledge (accessed September 1, 2015).

U.S. Department of Defense

The DoD’s Ovarian Cancer Research Program (OCRP) 8 received congressional appropriations from FY 1997 to FY 2014 totaling $236.45 million and received another $20 million in appropriations for FY 2015 (DoD, 2015a). Since the inception of the DoD OCRP, more than 130 ovarian cancer survivors have taken part in efforts to establish the OCRP’s priorities and research award mechanisms, and they have helped choose the research to be funded. From FY 1997 through FY 2013, the OCRP funded 313 awards in a variety of areas (see Figure 1-13 ). These awards show a focus on biology, treatment, and early detection, diagnosis, and prognosis. OCRP’s research priorities include understanding the precursor lesions, microenvironment, and pathogenesis of all types of ovarian cancer; developing and improving the performance and reliability of screening, diagnostic approaches, and treatment; developing or validating models to study initiation and progression; investigating tumor response to therapy; and enhancing the pool of ovarian cancer scientists (DoD, 2015a).

National Institutes of Health

The NCI of the NIH has initiated several activities to advance ovarian cancer research with intramural and extramural funding. In the past, five ovarian cancer–specific specialized programs of research excellence (SPOREs) in the United States conducted ovarian cancer research in early detection, imaging technologies, risk assessment, immunosuppression, and novel therapeutic approaches (NCI, 2015e). The NCI currently lists four active SPOREs for ovarian cancer.

The NCI is involved in ovarian cancer research in a variety of other ways. For example, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) is trying to understand the molecular basis of cancer in order to help improve the diagnosis, treatment, and prevention of cancer (NCI, 2015b). To accomplish these goals, CPTAC is using the data collected by The Cancer Genome Atlas (TCGA) analysis of ovarian tumors. The NCI has also supported a follow-up of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to analyze the biological material and risk factor information in order to better understand the risks and identify early biomarkers, including biomarkers for ovarian cancers. (See Chapter 3 for more on the PLCO Cancer Screening Trial.)

8 For more information, see http://cdmrp.army.mil/ocrp (accessed July 21, 2015).

FIGURE 1-13 Areas of ovarian cancer research funded by OCRP, FY 1997–2011. SOURCE: DoD, 2015b.

Overall, the NCI supported $100.6 million in research 9 related to ovarian cancer in FY 2013 while providing $559.2 million for breast cancer research, $63.4 million for cervical cancer research, and $17.8 million for endometrial cancer research (NCI, 2015g). However, the research projects listed as being related to ovarian cancer are not necessarily limited to ovarian cancer, and they include studies of multiple cancers (including ovarian cancer) or areas of cross-cutting research related to ovarian cancer. Fur-

9 The NCI notes that “the estimated NCI investment is based on funding associated with a broad range of peer-reviewed scientific activities” (NCI, 2015g). The NCI research portfolio for ovarian cancer may be found at http://fundedresearch.cancer.gov/nciportfolio/search/get?site=Ovarian+Cancer&fy=PUB2013 (accessed December 2, 2015).

thermore, data collected by the DoD 10 through the International Cancer Research Partnership indicates that the funded amount is significantly less when considering only new grants awarded by the NCI each year. Only 52 projects involving ovarian cancer research totaling $33.4 million were started in 2010, 58 new projects totaling $20.4 million in 2011, and 52 new projects totaling $16.3 million in 2012 (ICRP, 2015). Figure 1-14 shows that, like the DoD, the NCI portfolio for ovarian cancer research focuses primarily on treatment, biology, and early detection, diagnosis, and prognosis.

The Office of Cancer Survivorship (OCS), 11 part of the Division of Cancer Control and Population Sciences at the NCI, “works to enhance the quality and length of survival of all persons diagnosed with cancer and to minimize or stabilize adverse effects experienced during cancer survivorship. The office supports research that both examines and addresses the long- and short-term physical, psychological, social, and economic effects of cancer and its treatment among pediatric and adult survivors of cancer and their families” (NCI, 2014).

Figure 1-15 shows the areas of cancer survivorship research expertise at the NCI. As of October 2015, the Division of Cancer Control and Population Sciences had two open funding opportunities for general cancer survivorship research: one focused on the efficacy and impact of care planning, and the other examined the effects of physical activity and weight control interventions on cancer prognosis and survival (NCI, 2015a). Neither of these grant opportunities specified a focus on ovarian cancer survivorship.

Private Stakeholders

A wide variety of private stakeholders are engaged in ovarian cancer research, including professional societies, advocacy organizations, women’s health groups, and disease-specific foundations. In some cases, the organization specifically focuses on ovarian cancer and ovarian cancer research. However, many others focus on cancer or women’s health broadly (e.g., the American Cancer Society and the American Congress of Obstetricians and Gynecologists). Overall, private funders of ovarian cancer research tend to focus funding on biology and treatment, with very little funding directed toward the etiology of ovarian cancer or survivorship issues.

Private stakeholders can support young researchers with grant funding; provide training and educational opportunities; encourage collabora-

10 Personal communication, Patricia Modrow, data assembled by the U.S. Department of Defense Ovarian Cancer Research Program, January 16, 2015.

11 For more information about the OCS, see http://cancercontrol.cancer.gov/ocs (accessed May 15, 2015).

FIGURE 1-14 Areas of ovarian cancer research funded by the NCI. SOURCE: NCI, 2013.

tive, transdisciplinary efforts; and engage consumers, survivors, and their families. Examples of previous and current efforts by individual private stakeholders include

• The Health, Empowerment, Research, and Awareness Women’s Cancer Foundation awarded the Sean Patrick Multidisciplinary Collaborative Grant for cross-disciplinary projects to allow scientists to come together and test ideas that may not be fundable by other agencies (HERA, 2015).
• The Marsha Rivkin Center for Ovarian Cancer Research awards Bridge Funding Awards to researchers who are close to fundable grant scores for the DoD or the NIH but require additional data to ensure a successful resubmission (Rivkin Center, 2015).
• The Ovarian Cancer Research Fund (OCRF) provides funding to researchers at all stages of their careers; OCRF awards include funding for recent graduates, newly independent researchers who are building laboratories, and senior researchers working on collaborative projects (OCRF, 2015).

FIGURE 1-15 Expertise areas for cancer survivorship research at the NCI. SOURCE: NCI, 2015c.

• The Society of Gynecologic Oncology (SGO) released Pathways to Progress in Women’s Cancer in 2011, a research agenda based on discussions of working groups at a 2010 research summit. One working group focused on ovarian cancers, and the report provides short-term, intermediate, and long-term research priorities (SGO, 2011).
• The Honorable Tina Brozman Foundation for Ovarian Cancer Research (also known as Tina’s Wish) funds research specifically in the early detection and prevention of ovarian cancer and also supports a consortium to advance such research (Tina’s Wish, 2015).

The Role of Advocacy in Ovarian Cancer Research

Advocacy has positively affected ovarian cancer research, public knowledge, and awareness. Many different types of people play the role of

advocate—women with ovarian cancer, partners, family members, health care professionals, and activists—and their advocacy efforts range from the individual, patient level to the societal level, but all of these different efforts have had effects on funding efforts, policy change, and the direction of research.

Patients self-advocate by taking active roles in their own care. Researchers have recognized this concept of self-advocacy as an important part of patient-centered care, and it has been described as “a distinct type of advocacy in which an individual or group supports and defends their interests either in the face of a threat or proactively to meet their needs” (Hagan and Donovan, 2013, p. 3). However, despite claims that self-advocacy may improve quality of life, health care use, and symptom management, these potential effects have not been adequately studied.

Nurses can serve as advocates for patients by protecting patients’ rights, incorporating patients’ beliefs and values into their care plans, and respecting the autonomy of the patient to ensure access to quality care (Temple, 2002). Advocacy groups provide education, information, and personal support to patients, family caregivers, and the general public. Many advocacy groups also use lobbying efforts to influence policy, including the direction of research and funding.

Large-scale advocacy efforts have arguably had a great impact on cancer research and funding. In the late 1990s, survivors advocated for wider recognition of early-stage ovarian cancer symptoms. Until that time, physicians and medical textbooks had claimed that women did not experience symptoms until advanced stages of disease (Twombly, 2007). Johanna’s Law is considered a victory of advocacy groups’ lobbying efforts. Furthermore, Congress has appropriated funds for ovarian cancer research and education programs since FY 1997. The establishment and unified efforts of national advocacy organizations are partially responsible for the significant funding increases in the intervening years (Temple, 2002).

Advocacy groups have also been integral to the advancement of ovarian cancer research through their participation in the design and administration of studies (Armstrong et al., 2014; Holman et al., 2014). The scientific literature emphasizes the importance of patient advocates in patient-centered research, citing examples of the collaboration between researchers and patient advocates in research studies (Armstrong et al., 2014; Holman et al., 2014; Staton et al., 2008).

Several large advocacy groups at the national and international levels focus on ovarian cancer. For example, the Ovarian Cancer National Alliance (OCNA), a national advocacy organization, has among its activities the Survivors Teaching Students: Saving Women’s Lives® program, which is aimed at educating caregivers and medical, nursing, and other professional

students about the early signs and symptoms of ovarian cancer. Recently, OCNA spearheaded the formation of the first congressional Ovarian Cancer Caucus with the support of Rosa DeLauro (D-CT) and Sean Duffy (R-WI). The first meeting was held on September 29, 2015, in Washington, DC. The National Ovarian Cancer Coalition (NOCC), another national advocacy organization, funds the Teal Initiative to improve education and awareness. NOCC also supports specific research in ovarian cancer and provides survivor support, primarily through its Faces of Hope program, which is “dedicated to improving the quality of life for women affected by ovarian cancer, as well as providing support for their loved ones and caregivers” (NOCC, 2014). At the international level, the charity Ovarian Cancer Action encourages collaboration among ovarian cancer researchers around the world. Half of its funds go to the Ovarian Cancer Action Research Centre in the United Kingdom, which exclusively supports “research that can be translated into meaningful outcomes for real women in real life” (Ovarian Cancer Action, 2015). In addition, every few years Ovarian Cancer Action hosts an international forum to bring researchers together to share information, inspire collaboration, and develop white papers. In 2011 the forum developed the paper Rethinking Ovarian Cancer: Recommendations for Improving Outcomes, which outlined recommendations for improving outcomes for women with ovarian cancer (Vaughan et al., 2011). A number of other advocacy groups work at the local and national levels to support research in ovarian cancer.

The Role of Consortia and Collaboration in Ovarian Cancer Research

Because of the relative rarity of ovarian cancers, especially when subdivided according to subtypes, collaborative research efforts are necessary in order to collect sufficient data for statistically significant results. Many consortia and multisite studies have evolved to promote the sharing of biospecimens, clinical data, and epidemiologic data in order to ensure sufficient sample sizes in studies. These consortia and collaborations operate at both the national and international levels. Common uses of consortia include carrying out research on the genetic and nongenetic risk factors of developing ovarian cancers, studying mechanisms of disease relapse and resistance, and identifying newer therapies (AOCS, 2015; COGS, 2009; NRG Oncology, 2015; OCAC, 2015; OCTIPS, 2015). Furthermore, groups will often team together in coalitions to promote transdisciplinary research and also to promote the translation and dissemination of information. For example, in 2015, OCNA, NOCC, and OCRF provided funding for the Stand Up To Cancer (SU2C) Dream Team for ovarian cancer. This team will bring together experts in DNA repair, translational investigators, and

clinicians “to create new programs in discovery, translation, and clinical application, while cross-fertilizing and educating researchers at all levels to enhance collaboration and catalyze translational science” (SU2C, 2015).

Consortia and coalitions have had clear, measureable impacts on the research base for ovarian cancers. For example, as a result of the Collaborative Oncological Gene-environment Study (COGS), 14 new markers for risk of ovarian cancer were identified (only 8 had been known before COGS) (COGS, 2014). Based on the work of this coalition, TCGA researchers completed a detailed analysis of ovarian cancer, which confirmed that mutations in the TP53 gene (which encodes a protein that normally suppresses tumor development) are present in nearly all HGSCs (Bell et al., 2011). The analysis also examined gene expression patterns and identified signatures that correlate with survival outcomes, affirmed four subtypes of HGSCs, and identified dozens of genes that might be targeted by gene therapy (NIH, 2011, 2015b).

NCI’s National Clinical Trials Network

In 1955 the NCI established the Clinical Trials Cooperative Group Program. As the science of cancer treatment was evolving, researchers realized that collaborative efforts were necessary to accrue sufficient numbers for clinical trials in order to more rapidly compare the value of new therapies to existing standards of care, particularly for the use of chemotherapy in the treatment of solid tumors (DiSaia et al., 2006; IOM, 2010b). The work of the cooperative groups led to advances in the treatment of women with ovarian cancer specifically, including a demonstration of the value of adding paclitaxel to cisplatin, confirmation of the value of cytoreductive surgery, and a demonstration of the value of carboplatin for late-stage ovarian cancers (IOM, 2010b). The groups have also studied issues related to the quality of life and the prevention of ovarian cancer. Between 1970 and 2005, clinical trials of the Gynecologic Oncology Group (GOG) alone included approximately 35,000 women with ovarian cancer (DiSaia et al., 2006).

In 2014, based in part on the IOM report A National Cancer Clinical Trials System for the 21st Century , the NCI transformed the cooperative group program into the new National Clinical Trials Network (IOM, 2010b, 2011, 2013b; NCI, 2015f). This reorganization consolidated nine cooperative groups into five new groups:

• The Alliance for Clinical Trials in Oncology;
• The ECOG-ACRIN Cancer Research Group (a merger of two cooperative groups: the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network);
• NRG Oncology (a merger of three cooperative groups: the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the GOG);
• The Southwest Oncology Group; and
• The Children’s Oncology Group (NCI, 2015f).

PREVIOUS WORK AT THE INSTITUTE OF MEDICINE

The IOM has a long history of producing reports related to various aspects of cancer care, and many of them are directly relevant to this current study. This section describes some examples of previous IOM work that is related to the work of this committee.

Prevention and Early Detection

In 2005 the IOM report Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis (IOM, 2005) recommended the development of tools to identify the women who would benefit most from breast cancer screening based on “individually tailored risk prediction techniques that integrate biologic and other risk factors.” The report also called for the development of tools that “facilitate communication regarding breast cancer risk to the public and to health care providers.” In addition, the report called for more research on breast cancer screening and detection technologies, including research on various aspects of technology adoption (e.g., monitoring the use of technology in clinical practice).

A 2007 IOM report, Cancer Biomarkers , offered recommendations on the methods, tools, and resources needed to discover and develop biomarkers for cancer; guidelines, standards, oversight, and incentives needed for biomarker development; and the methods and processes needed for clinical evaluation and adoption of such biomarkers (IOM, 2007a). Specific recommendations from the report included establishing international consortia to generate and share data, supporting high-quality biorepositories of prospectively collected samples, and developing criteria for conditional coverage of new biomarker tests. Subsequently, in 2010, an IOM report, Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease , outlined a framework for the evaluation of biomarkers (IOM, 2010a).

In Initial National Priorities for Comparative Effectiveness Research (IOM, 2009), the committee offered two priorities that are relevant to ovarian cancer genetics: “Compare the effectiveness of adding informa-

tion about new biomarkers (including genetic information) with standard care in motivating behavior change and improving clinical outcomes” and “Compare the effectiveness of genetic and biomarker testing and usual care in preventing and treating breast, colorectal, prostate, lung, and ovarian cancer, and possibly other clinical conditions for which promising biomarkers exist” (IOM, 2009, p. 4).

In 2007, the IOM’s National Cancer Policy Forum hosted a workshop on cancer-related genetic testing and counseling. According to the published summary of that workshop, participants observed that “genetic testing and counseling are becoming more complex and important for informing patients and families of risks and benefits of certain courses of action, and yet organized expert programs are in short supply. The subject matter involves not only the scientific and clinical aspects but also workforce and reimbursement issues, among others” (IOM, 2007b)

Clinical Trials

The 2005 IOM report on breast cancer detection called for public health campaigns and for improved information and communication about the value of participation in clinical trials (including the participation of healthy individuals).

A 2010 report, A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program (IOM, 2010b), called for the restructuring of the NCI Cooperative Group Program and set four goals:

• Improve the speed and efficiency of the design, launch, and conduct of clinical trials (e.g., improve collaboration among stakeholders);
• Incorporate innovative science and trial design into cancer clinical trials (e.g., support standardized central biorepositories, develop and evaluate novel trial designs);
• Improve the means of prioritization, selection, support, and completion of cancer clinical trials (e.g., develop national unified standards); and
• Incentivize the participation of patients and physicians in clinical trials (e.g., develop electronic tools to alert clinicians to available trials for specific patients, encourage eligibility criteria to allow broad participation, cover cost of patient care in trials).

Palliative and End-of-Life Care

Improving Palliative Care for Cancer (IOM, 2001) called for incorporating palliative care into clinical trials. The report also noted that infor-

mation on palliative and end-of-life care is largely absent from materials developed for the public about cancer treatment, and the committee recommended strategies for disseminating information and improving education about end-of-life care. The report recommended that the NCI require comprehensive cancer centers to carry out research in palliative care and symptom control and that the Health Care Finance Administration (now the Centers for Medicare & Medicaid Services) fund demonstration projects for service delivery and reimbursement that integrate palliative care throughout the course of the disease.

Dying in America (IOM, 2015) noted that palliative care can begin early in the course of treatment, in conjunction with treatment, and can continue throughout the continuum of care. The report further observed that “a palliative approach can offer patients near the end of life and their families the best chance of maintaining the highest possible quality of life for the longest possible time” (IOM, 2015, p. 1).

Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis (IOM, 2013a) addressed the delivery of cancer care, including palliative and end-of-life care. The study called for providing patients and their families with understandable information about palliative (and other) care and recommended that “the cancer care team should provide patients with end-of-life care consistent with their needs, values, and preferences” (IOM, 2013a, p. 9).

Communication and Survivorship

From Cancer Patient to Cancer Survivor (IOM, 2006) called for actions to raise awareness about the needs of cancer survivors, including the establishment of cancer survivorship as a distinct phase of cancer care. In 2008, the IOM report Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs (IOM, 2008) recommended that facilitating effective communication between patients and care providers, identifying psychosocial health needs, and engaging and supporting patients in managing their illnesses should all be considered as part of the standard of care. The report emphasized the importance of educating patients and their families and of enabling patients to actively participate in their own care by providing tools and training in how to obtain information, make decisions, solve problems, and communicate more effectively with their health care providers. The report further called for the government to invest in a large-scale demonstration and evaluation of various approaches to the efficient provision of psychosocial health care.

Women’s Health Research (IOM, 2010c) found that there are many barriers to the translation of research findings in general and that some have aspects that are “peculiar to women.” The committee recommended

specific research on how to translate research findings on women’s health into clinical practice and public health policies.

Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis (IOM, 2013a) called for providing patients and their families with “understandable information on cancer prognosis, treatment benefits and harms, palliative care, psychosocial support, and estimates of the total and out-of-pocket costs of cancer care.” The report further called for the development of decision aids to be made available through print, electronic, and social media; for the formal training of cancer care team members in communication; for the communication of relevant and personalized information at key decision points along the continuum of cancer care; and for consideration of patients’ individual needs, values, and preferences when developing a care plan, including end-of-life care. The report also called for the identification and public dissemination of evidence-based information about cancer care practices that are unnecessary or for which the harm may outweigh the benefits.

OVERVIEW OF THE REPORT

This chapter has provided an overview of the study charge and the committee’s approach to its work. It has also provided an introduction to the challenges in ovarian cancer research, to defining and classifying ovarian cancers, to the patterns and demographics of the disease, and to the landscape of stakeholders in ovarian cancer research. The remaining chapters follow the research framework outlined in Figure 1-1 .

Chapter 2 describes the current state of the science in the biology of ovarian cancers, thus providing a foundation for the descriptions of most of the other ovarian cancer research covered in this report. This background includes information about the characteristics of specific ovarian carcinomas, the role of the tumor microenvironment, and experimental model systems.

Chapter 3 builds on this to discuss research on the prevention and early detection of ovarian cancers. On the topic of risk assessment, the chapter includes discussions of a wide range of genetic and nongenetic risk factors for the development of an ovarian cancer, risk-prediction models, and genetic testing. Concerning prevention, both surgical and nonsurgical prevention strategies are discussed. And on the topic of early detection, the chapter has descriptions of various approaches to identifying ovarian cancers earlier, including biomarkers and imaging techniques, and a discussion of the challenges in performing screening in both general and high-risk populations.

Chapter 4 describes the research base for the diagnosis and treatment of women newly diagnosed with ovarian cancer as well as for women with

relapsed ovarian cancer. The chapter outlines research on current standards of care and also explores the development of novel therapeutics such as anti-angiogenics, poly ADP ribose polymerase (PARP) inhibitors, and immunotherapy. Later, the chapter discusses issues of clinical trial development and use as they relate specifically to research in ovarian cancer.

Chapter 5 discusses research on survivorship and management issues along the entire care continuum from diagnosis to end of life. Furthermore, women who are at a high risk for developing cancer (sometimes referred to as “previvors”) may have psychosocial needs of their own that should be studied. Overall, research that focuses specifically on survivorship and management issues in ovarian cancer is scarce; it may thus be necessary to apply research from broader studies of survivorship to women with ovarian cancer. The chapter discusses the research base for the unique issues of survivorship and management for women with ovarian cancer and their families, including managing the physical side effects of treatment, addressing unique psychosocial impacts, engaging women in their own self-care, and addressing end-of-life concerns.

Chapter 6 summarizes the findings and conclusions of the previous chapters in order to provide a cohesive set of recommendations for prioritizing research on ovarian cancers in such a way as to have the greatest impact on reducing morbidity and mortality from the disease.

Chapter 7 gives an overview of research on the translation and dissemination of new information to the general public, providers, researchers, policy makers, and others. The chapter reflects on the messages within the previous chapters that are ready to be communicated and identifies potential avenues for communicating these messages.

Finally, the report contains five appendixes. Appendix A contains a list of key acronyms used throughout the report. Appendix B contains a glossary of key terms. Appendix C includes a listing of currently active studies on epithelial ovarian cancer (based on information available through www.ClinicalTrials.gov ) in order to give a sense of where emphasis is being placed in future research. Appendix D lists the agendas of the committee’s workshops. Appendix E contains the biographical sketches of the committee members and project staff.

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In an era of promising advances in cancer research, there are considerable and even alarming gaps in the fundamental knowledge and understanding of ovarian cancer. Researchers now know that ovarian cancer is not a single disease—several distinct subtypes exist with different origins, risk factors, genetic mutations, biological behaviors, and prognoses. However, persistent questions have impeded progress toward improving the prevention, early detection, treatment, and management of ovarian cancers. Failure to significantly improve morbidity and mortality during the past several decades is likely due to several factors, including the lack of research being performed by specific disease subtype, lack of definitive knowledge of the cell of origin and disease progression, and incomplete understanding of genetic and non-genetic risk factors.

Ovarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines avenues for translation and dissemination of new findings and communication of new information to patients and others. This study makes recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of morbidity and mortality from ovarian cancers.

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Ovarian Cancer: An Integrated Review

Affiliations.

• 1 Carolina's Medical Center, Charlotte, NC. Electronic address: [email protected].
• 2 Assistant Vice President Patient Care Services, Carolina's Medical Center, Rock Hill, SC.
• 3 Interim Dean, Harris College of Nursing & Health Sciences, Associate Dean for Nursing & Professor, Texas Christian University, Ft Worth, TX.
• PMID: 30867104
• DOI: 10.1016/j.soncn.2019.02.001

Objective: To provide an overview of the risk factors, modifiable and non-modifiable, for ovarian cancer as well as prevention, diagnostic, treatment, and long-term survivorship concerns. This article will also examine current and future clinical trials surrounding ovarian cancer.

Data sources: A review of articles dated 2006-2018 from CINAHL, UpToDate, and National Comprehensive Cancer Network guidelines.

Conclusion: There is no screening test for ovarian cancer and with diagnosis often in the late stages, recurrence is high in this population. Early identification can range from knowing the vague symptoms associated with the cancer to prophylactic surgical removal of at-risk tissue. Standard treatment for ovarian cancer is surgery followed by combination chemotherapy. Although advances are being made, ovarian cancer remains the most fatal female gynecologic cancer.

Implications for nursing practice: Becoming familiar with and educating women about risk factors and the elusive symptoms of ovarian cancer can increase patient autonomy and advocacy, as well as potentially improve patient outcomes for those affected by ovarian cancer.

Keywords: BRCA; gynecologic; oncology; ovarian cancer; prevention; risk factors.

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PERFLUOROALKYL SUBSTANCES (PFAS) INDUCED THERAPY RESISTANCE IN OVARIAN CANCER AND INTERVENTION VIA PHOTOCHEMICAL TARGETING OF MITOCHONDRIA

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• Affiliation: School of Medicine, Curriculum in Toxicology
• One of the main contributors to the lethality of ovarian cancer is resistance tochemotherapy, which occurs in ~85% of patients. Chemotherapy resistance can be innate or canresult from internal (i.e. ascites) or external (i.e. environmental contaminants) exposures.Perfluoroalkyl substances (PFAS) are widespread environmental contaminants that pollutedrinking water supplies worldwide. These chemicals have been linked to adverse reproductivehealth effects in women, including infertility. In a study evaluating the effects of short-term (48-hour) PFAS exposure on ovarian cancer cell chemotherapy response, several PFAS and PFASmixtures were associated with increased survival post-carboplatin treatment, indicative ofchemotherapy resistance. A concomitant increase in mitochondrial membrane potential (ΔΨm)was also observed, suggestive of a mitochondrial mode of action for PFAS-inducedchemoresistance. Impacts of PFAS on mitochondrial functioning were further explored in astudy comparing the effects of short-term, long-term (144-hour), and chronic (26-day) PFASexposures. After long-term exposure, the production of superoxide significantly increased.Significant increases in chemotherapy resistance and ΔΨm were observed in ovarian cancer cellsthat were chronically exposed to PFAS, compared to short-term exposures. These findingsimplicate mitochondria as potential targets of PFAS exposure in ovarian cancer cells.Photodynamic priming (PDP) is a light-based treatment approach that has shown promise in thecontext of ovarian cancer. Importantly, photosensitizers used for PDP, such as aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) or benzoporphyrin derivative (BPD) are, in part,synthesized in or preferentially localize to, mitochondria. Subsequent light activation leads to theproduction of reactive molecular species and localized photodamage, including to themitochondrial membrane. In ovarian cancer cells exposed to short-term PFAS, treatment witheither BPD- or ALA-PpIX-PDP in combination with carboplatin significantly reduced survivalin all groups where chemotherapy resistance was observed. ΔΨm also decreased significantly inPFAS-exposed ovarian cancer cells treated with mitochondria-associated PDP, suggesting thatdiminishing mitochondrial health is key to overcoming PFAS-induced chemotherapy resistance.Collectively, these data highlight the ability of PFAS to alter response to chemotherapy inovarian cancer cells, propose the mitochondrion as a target of PFAS-induced effects, anddemonstrate the efficacy of mitochondria-associated PDP as a therapeutic approach to overcomeenvironmental contaminant-induced chemotherapy resistance.
• Photodynamic therapy
• Mitochondria
• Chemotherapy resistance
• Ovarian cancer
• https://doi.org/10.17615/sfe1-mx20
• Dissertation
• In Copyright - Educational Use Permitted
• Rizvi, Imran
• Fenton, Suzanne E
• Fry, Rebecca C
• Bae-Jump, Victoria L
• Kenny, Hilary A
• Doctor of Philosophy
• University of North Carolina at Chapel Hill Graduate School

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Pretreatment with or without GnRH-agonist before frozen–thawed embryo transfer in patients with PCOS: a systematic review and meta-analysis

This study was aimed to systematically evaluate the efficacy of artificial cycle-prepared frozen–thawed embryo transfer (FET) with or without gonadotrophin-releasing hormone agonist (GnRH-a) pretreatment for w...

Amplifications of EVX2 and HOXD9-HOXD13 on 2q31 in mature cystic teratomas of the ovary identified by array comparative genomic hybridization may explain teratoma characteristics in chondrogenesis and osteogenesis

Teratomas are a common type of germ cell tumor. However, only a few reports on their genomic constitution have been published. The study of teratomas may provide a better understanding of their stepwise differ...

Combined analysis of estradiol and β-hCG to predict the early pregnancy outcome of FET: a retrospective study

The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E 2 ) and β-hCG concentrations ...

The experıance of tertıary center for adult granulosa cell tumor: whıch factors predıct survival?

This retrospective study aims to evaluate the clinical course and long-term outcomes of patients diagnosed with adult granulosa cell tumors (AGCT).

High expression levels of centromere protein O participates in cell proliferation of human ovarian cancer

Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence ...

Autoimmune thyroid disease and ovarian hypofunction: a review of literature

Thyroid hormones(THs) are essential for the proper functioning of the ovaries, and multiple studies have shown that thyroid abnormalities, especially during adolescence and reproductive age, can lead to lifelo...

HOXB2 promotes cisplatin resistance by upregulating lncRNA DANCR in ovarian cancer

Ovarian cancer (OV) is a highly fatal malignant disease that commonly manifests at an advanced stage. Drug resistance, particularly platinum resistance, is a leading cause of treatment failure because first-li...

Correction: Alteration of the N 6 ‑methyladenosine methylation landscape in a mouse model of polycystic ovary syndrome

The original article was published in Journal of Ovarian Research 2023 16 :157

DNA methylation profiles of ovarian cysts resemble ovarian tissues but not endometrial tissues

Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still u...

Enhancing angiogenesis and inhibiting apoptosis: evaluating the therapeutic efficacy of bone marrow mesenchymal stem cell-derived exosomes in a DHEA-induced PCOS mouse model

Polycystic Ovary Syndrome (PCOS) is a widespread endocrine disorder among women, characterized by symptoms like ovarian cysts, hormonal imbalance, and metabolic issues. This research evaluates the therapeutic ...

In vitro matured oocytes have a higher developmental potential than in vivo matured oocytes after hormonal ovarian stimulation in Callithrix jacchus

The common marmoset, Callithrix jacchus , is an invaluable model in biomedical research. Its use includes genetic engineering applications, which require manipulations of oocytes and production of embryos in vitro...

Exploration and prognostic analysis of two types of high-risk ovarian cancers: clear cell vs. serous carcinoma: a population-based study

Ovarian clear cell carcinoma (OCCC) is a rare pathological histotype in ovarian cancer, while the survival rate of advanced OCCC (Stage III-IV) is substantially lower than that of the advanced serous ovarian c...

Ovarian aging: energy metabolism of oocytes

In women who are getting older, the quantity and quality of their follicles or oocytes and decline. This is characterized by decreased ovarian reserve function (DOR), fewer remaining oocytes, and lower quality...

What is the optimal number of embryos to transfer for POSEIDON group 1 and group 2? A retrospective study

The 2016 Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria redefined the poor responders as low prognosis patients. The embryo transfer strategy for POSEIDON patients rema...

Development and validation of a prediction model for suboptimal ovarian response in polycystic ovary syndrome (PCOS) patients undergoing GnRH-antagonist protocol in IVF/ICSI cycles

PCOS patients with unexpectedly low oocyte yield following conventional ovarian stimulation are referred to as suboptimal responders. However, identifying suboptimal responders presents a significant challenge...

Zinc deficiency deteriorates ovarian follicle development and function by inhibiting mitochondrial function

Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individual...

Value of estrogen pretreatment in patients with diminished ovarian reserve and elevated FSH on a line antagonist regimen: a retrospective controlled study

The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS), especially in patients with diminished ...

Exosomes in diagnostic and therapeutic applications of ovarian cancer

Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic...

Correction: A methylation‑ and immune‑related lncRNA signature to predict ovarian cancer outcome and uncover mechanisms of chemoresistance

The original article was published in Journal of Ovarian Research 2023 16 :186

Examining the oleoylethanolamide supplement effects on glycemic status, oxidative stress, inflammation, and anti-mullerian hormone in polycystic ovary syndrome

This clinical trial was designed and conducted due to the anti-inflammatory potential of Oleoylethanolamide (OEA) to examine the effect of OEA supplement on glycemic status, oxidative stress, inflammatory fact...

Analysis of prognostic value of lactate metabolism-related genes in ovarian cancer based on bioinformatics

Recent studies have provided evidence supporting the functional role and mechanism of lactate in suppressing anticancer immunity. However, there is no systematic analysis of lactate metabolism-related genes (L...

Correction: Effect of blastocyst shrinkage on assisted reproductive outcomes: a retrospective cohort study describing a new morphological evaluation of blastocyst pre-vitrification and post-warming

The original article was published in Journal of Ovarian Research 2023 16 :192

Alkali and alkaline earth elements in follicular fluid and the likelihood of diminished ovarian reserve in reproductive-aged women: a case‒control study

Imbalances in alkali elements (AEs) and alkaline earth elements (AEEs) cause reproductive disorders. However, it remains unclear whether AEs/AEEs in follicular fluid have a relationship with the serious reprod...

Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction

Abnormal granulosa cell (GC) death contributes to cyclophosphamide (CTX) induced primary ovarian insufficiency (POI). To investigate the contribution of GCs to POI, gene profiles of GCs exposed to CTX were ass...

Correlation between anti-mullerian hormone with insulin resistance in polycystic ovarian syndrome: a systematic review and meta-analysis

Epidemiological studies regarding the correlation between anti-Müllerian hormone (AMH) and insulin resistance (IR) in polycystic ovarian syndrome (PCOS) remain inconsistent. The primary aim of this study was t...

Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization

In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hype...

Platelet-rich plasma (PRP) treatment of the ovaries significantly improves fertility parameters and reproductive outcomes in diminished ovarian reserve patients: a systematic review and meta-analysis

The incidence of infertility caused by diminished ovarian reserve has become a significant problem worldwide. The beneficial effect of PRP treatment of the ovaries has already been described, but the high-leve...

Correlation of FMR4 expression levels to ovarian reserve markers in FMR1 premutation carriers

Fragile X-associated primary ovarian insufficiency (FXPOI), characterized by amenorrhea before age 40 years, occurs in 20% of female FMR1 premutation carriers. Presently, there are no molecular or biomarkers that...

Proto-oncogene c-Myb potentiates cisplatin resistance of ovarian cancer cells by downregulating lncRNA NKILA and modulating cancer stemness and LIN28A-let7 axis

Ovarian cancer is a major gynecological cancer that has poor prognosis associated mainly to its late diagnosis. Cisplatin is an FDA approved ovarian cancer therapy and even though the therapy is initially prom...

Shikonin reduces M2 macrophage population in ovarian cancer by repressing exosome production and the exosomal galectin 3-mediated β-catenin activation

Shikonin (SK), a naphthoquinone with anti-tumor effects, has been found to decrease production of tumor-associated exosomes (exo). This study aims to verify the treatment effect of SK on ovarian cancer (OC) ce...

Interlukin-22 improves ovarian function in polycystic ovary syndrome independent of metabolic regulation: a mouse-based experimental study

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder with multiple metabolic abnormalities. Most PCOS patients have concomitant metabolic syndromes such as insulin resistance and obesity, whic...

The landscape of transcriptional profiles in human oocytes with different chromatin configurations

With increasingly used assisted reproductive technology (ART), the acquisition of high-quality oocytes and early embryos has become the focus of much attention. Studies in mice have found that the transition o...

Ovarian Hyperstimulation syndrome combined with hypothyroidism: a comprehensive review

Ovarian Hyperstimulation Syndrome (OHSS) is a systemic condition marked by the enlargement of the ovaries and heightened vascular permeability. And hypothyroidism (HT) emerges as a potential risk factor for OH...

EGF-like growth factors upregulate pentraxin 3 expression in human granulosa-lutein cells

The epidermal growth factor (EGF)-like factors, comprising amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG), play a critical role in regulating the ovulatory process. Pentraxin 3 (PTX3), an essen...

Fertility-sparing surgery in children and adolescents with borderline ovarian tumors: a retrospective study

To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients.

Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study

Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain.

NB compounds are potent and efficacious FOXM1 inhibitors in high-grade serous ovarian cancer cells

Genetic studies implicate the oncogenic transcription factor Forkhead Box M1 (FOXM1) as a potential therapeutic target in high-grade serous ovarian cancer (HGSOC). We evaluated the activity of different FOXM1 ...

Correction: TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2

The original article was published in Journal of Ovarian Research 2024 17 :67

A novel defined programmed cell death related gene signature for predicting the prognosis of serous ovarian cancer

This study aims to explore the contribution of differentially expressed programmed cell death genes (DEPCDGs) to the heterogeneity of serous ovarian cancer (SOC) through single-cell RNA sequencing (scRNA-seq) ...

The effect of adipose-derived mesenchymal stem cell transplantation on ovarian mitochondrial dysfunction in letrozole-induced polycystic ovary syndrome in rats: the role of PI3K-AKT signaling pathway

The present study aimed to elucidate how mesenchymal stem cells (MSCs) application could efficiently attenuate pathological changes of letrozole-induced poly cystic ovary syndrome (PCOS) by modulating mitochon...

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Ovarian Cancer Essays (Examples)

62+ documents containing “ovarian cancer” .

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Ovarian cancer what exactly is.

A mutation of the gene causing colorectal cancer or epithelial ovarian cancer are major risk factors for ovarian cancer, and genetic testing within the laboratory can identify most of these. However, the women who possess these inherited genes are at less risk than those women who do not have any family history of ovarian cancer, and while the former group can be treated with advanced planning and genetic counseling, the latter group cannot be prepared in this manner. (What are the risk factors of ovarian cancer?) Some women who have already suffered from breast cancer at an earlier stage in their lives may be at increased risk for ovarian cancer because the reproductive organs are somehow connected with each other, and the inherited breast cancer gene, that is the BCA1 or the BCA2, drastically increases the risk factor for ovarian cancer. Some studies have indicated that those women, who use….

Define Cancer. Retrieved at  http://www.google.co.in/search?hl=en&lr=&oi=defmore&q=define:cancerAccessed  on 27 January, 2005

Dolson, Laura. The whisperings of ovarian cancer. Retrieved at http://www.baymoon.com/~gyncancer/library/weekly/aa011001a.htm. Accessed on 27 January, 2005

Oncology Channel, Ovarian Cancer. August 24, 2004. Retrieved at http://www.oncologychannel.com/ovariancancer/. Accessed on 27 January, 2005

Ovarian Cancer: National Cancer Institute. Retrieved at  http://www.nci.nih.gov/cancertopics/types/ovarianAccessed  on 27 January, 2005

Women's Health Issue Ovarian Cancer

These include bloating, abdominal or pelvic pain, frequent and/or urgent urination, and difficulty eating because one feels very full very quickly (MedicineNet, 2009). However, these were only agreed upon in 2007 and not all doctors feel that these are the best markers of ovarian cancer (MedicineNet, 2009). A lot of women experience at least the first two of these symptoms quite often during their menstrual cycle, and the others are not that uncommon, either. Women cannot be running to the doctor every time they have one small symptom, but a group of symptoms that appears and is persistent is certainly worth checking out, if only to provide peace of mind for a woman who may be worried about whether she has cancer or something much more benign (MedicineNet, 2009). Like many other cancers, ovarian cancer does seem to have some genetic link. In other words, if a lot of people….

MedicineNet (2009). Ovarian Cancer. Retrieved from:  http://www.medicinenet.com/ovarian_  cancer/article.htm

MedlinePlus (2009). Ovarian Cancer. U.S. National Library of Medicine. Retrieved from:  http://www.nlm.nih.gov/medlineplus/ovariancancer.html 

National Cancer Institute (2009). Ovarian Cancer. U.S. National Institutes of Health. Retrieved from:  http://www.cancer.gov/cancertopics/types/ovarian/

Plight of Ovarian Cancer Sufferers

usiness Research Terms and Concepts KNOWING THE DIFFERENCES Understanding Research Terms and Concepts Quantitative Research Methods and Instruments Quantitative research tests hypotheses from theories or approximates the magnitude of a particular phenomenon (Eau Claire, 2014). Participants or volunteers are assigned at random to different aspects or derive data from them to control their influence on a dependent variable. Probability sampling may be used if the intent is to generalize (Eau Claire). Quantitative data collection methods utilize and depend on random sampling and structured data collection instruments (Euau Claire, 2014). These methods and their instruments are suited to different anticipated types of responses. Their findings are easy to determine, summarize, analyze, compare and generalize. The most typical methods are experiments or clinical trials, observation and recording of a specific event, securing data from an entity's management information systems, and surveys with closed-ended questions. Surveys are conducted through interviews or questionnaires as instruments (Eau Claire). Interviews may be….

BIBLIOGRAPHY

Al-Benna, et al. (2010). Descriptive and inferential statistical methods used in Bruno research. Vol. 36 Issue 3, Burns: Elsevier. Retrieved on January 16. 2014 from  http://www.sciencedirect.com/science/article/pii/S030541790001405 

Brown, B.L. (2010). Descriptive statistics. Encyclopedia of Research Design: Sage

Journals. Retrieved on January 17, 2015 from http://www.srmo.sagepub.com/view/encyc-of-research-design/n111.xml

Eau Claire (2014). Quantitative and qualitative data collection methods. Wisconsin University Eau Claire. Retrieved on January 17, 2015 from  http://people.uwec.edu/piercech/ResearchMethods/Data%20collection%20methods/DATA%20COLLECTION%20METHODS.htm

Ovarian Cancer and Cancer

Phenoxodiol, a Medication for Cancer Clinical studies have predominantly focused on a couple of standard benzopyrans, namely flavopiridol and phenoxodiol (by Novogen, via MEI Pharma, the company's subsidiary at the time). Although a benzopyran, the former's method of action apparently differs from phenoxodiol's action neither of the two aforementioned benzopyrans has gained FDA (Food and Drug Administration) or EMA (European Medicines Agency) approval. The height of research on phenoxodiol was one 'Phase III' research on resistant cancer cells in the ovaries. Although slow recruitment led the trial at this phase to formally close down, results clearly displayed that oral consumption of phenoxodiol would most probably not have benefited patients, if the trial phase had been completed. Phenoxodiol results (in combination with others) led to the following hypothesis by Novogen: the problem with phenoxodiol pertained to bioavailability (in other words, the ingested drug wasn't reaching the site of cancer in adequate quantities);….

Marc Sinatra. (2015). Novogen Limited. Lodge Partners Research.

Marshall Edwards Inc.2003Investigational New Drug Status Cleared By FDA for Phenoxodiol in Oral Formpr Newswire

Paul Howard. (2015, November 1). Why The FDA Rejected A Drug That Helps Cure Lung Cancer -- And What We Can Do To Fix It. Forbes.

U.S. Department of Health and Human Services1998Guidance for Industryrockvillefood and Drug Administration

Care of Cancer Diagnosis in Many Cases

Care of Cancer Cancer diagnosis In many cases the sooner cancer is diagnosed and treatment begins the better the chances of a person recovering fully. If one develops cancer they can improve the chance of early detection if they have regular medical checkups and do some self-exams. Doctors often find early cancer during a physical exam or when carrying out routine tests even when there were no symptoms presented. There are several methods that are used to diagnose cancer .with technological advancement these methods are now better as they help in a better understanding of cancer .there are now many diagnostic tools that can be used in cancer detection. Once cancer I suspected a diagnosis is made by pathologists and oncopathologists and imaging radiologists. The common diagnostic methods are; Biopsy This test involves a small tissue sample being taken from the area where cancer is suspected using a fine tipped needle, surgical excision or….

Mandal, A.(2010). Cancer Diagnosis.Retrieved September 24,2013 from  http://www.news-medical.net/health/Cancer-Diagnosis.aspx 

American Society of Clinical Oncolog.(2013). Stages of Cancer. Retrieved September 24,2013 from  http://www.cancer.net/all-about-cancer/treating-cancer/stages-cancer 

Armstrong, B.(2012).What are the different stages of cancer and what do they mean? Retrieved September 24,2013 from http://www.cancerinstitute.org.au/patient-support/what-i-need-to-know/about-cancer/what-are-the-different-stages-of-cancer

Info.com.(2013).Cancer complications. Retrieved September 24,2013 from http://topics.info.com/Cancer-Complications_3416

Maturing From My Mom's Cancer

Maturing From My Mom's Cancer High School is a very difficult stage in any teenager's life. The experiences that one has to go through and the hurdles that need to be overcome can sometimes prove to be overwhelming. This is truly a challenging phase in any individual's life as they are growing up to face situations both on a social as well as a personal level. My story of acquiring a more mature outlook on life is no different. My transition into High School was not an easy one. From the beginning I had to face the fact that academics was not one of my strong sides. The grades which I achieved were near to average, something one should not be proud of. However, at the same time while I suffered on the academic front, my social life was doing well. In fact flourishing would be a more appropriate word to describe….

How to Cope With Cancer

Coping With Cancer According to the American Cancer Society, cancer is the second leading cause of death in the United States. Half of all men and one-third of all women in the U.S. will develop cancer during their lifetimes. oday, millions of people are living with cancer or have had cancer. he numbers are dismal; according to most statistical data American's possess almost a fifty percent chance of developing cancer. With these alarming statistics it is unfortunate and inevitable that almost everyone will have to in some way or another learn how face and cope with the depressing hardships and obstacles of cancer. Whether an individual is diagnosed personally with cancer or a friend or family member is, it seems as though all of us at some point in time may have to learn coping mechanisms for this illness. his paper addresses the various coping techniques that individuals can employ when dealing….

Telch, C.F. & Telch, M.J. "Group skills instruction and supportive group therapy for cancer patients: A comparison of strategies." Journal of Consulting and Clinical Psychology. 1966, 54, 802-808.

Kyngas, H.; Mikkonen, R. et al. Coping with the onset of cancer: coping strategies and resources of young people with cancer. European Journal of Cancer Care, Mar2001, Vol. 10 Issue 1, p6.

Coping with Cancer

Mechanisms of Cancer the Cancer

This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair" (Lakin 1999, p. 7644). In research led by Hussain, he investigated the targets of free radicals, which are DNA, proteins, NA, and lipids. He noted that, "mutations in cancer-related genes or post-translational modifications of proteins by nitration, nitrosation, phosphorylation, acetylation or polyADP-ribosylation-by free radiacals or lipid peroxidation byproducts…are some of the key events that can increase the cancer risk" (Hussain 2003, p. 276). Furthermore, changes in DNA occur when the person has been exposed to high levels of nitric oxide or NO. p53 plays a role in that it acts as a mediator to stress but NO "causes p53 accumulation and post-translational modifications that inhibit cellular growth" (Hussain 2003, p. 278). His research has revealed that when exposed to NO during chronic inflammation sans wild-type p53, there might be increased….

American Cancer Society (n.d.) Cancer Facts & Figures 2010, [online] Available at:  http://www.cancer.org/research/cancerfactsfigures/cancerfactsfigures/cancer-facts-and-figures-2010  [Accessed: April 19, 2011].

American Cancer Society (n.d.) What Causes Cancer?, [online] Available at:  http://www.cancer.org/Cancer/CancerCauses/index  [Accessed: April 19, 2011].

Croce, C. (2008) Oncogenes and Cancer, N Engl J. Med, 358, p. 502-511.

Hasty, P. (2005) the impact of DNA damage, genetic mutation and cellular responses on cancer prevention, longevity and aging: observations in humans and mice, Mech Ageing Dev, 126(1), p.71-77.

Body Mind and Soul in the Cancer Ward Wit

Body, Mind, and Soul in the Cancer Ward Margaret Edson’s Wit dramatizes the death of a literature professor from cancer. The play is designed to show the limits of the intellect to fully understand human tragedy and existence. Although the central protagonist Professor Vivian Bearin was a rigorous academic fluent in the works of John Donne when she was healthy, ultimately the fact her old English professor is able to provide her comfort during her dying moments by reading a children’s book provides her the greatest solace more than her philosophy and more than intellectualism. Bearin embarked upon an academic career because she was primarily interested in the life of the mind, not the body. The central irony of the play is that she is being killed by her own body with ovarian cancer. Ultimately, human beings are unable to escape the body in the form of death. The play is….

Breast Cancer Searching for the Mean Genes

cancer genes that are associated with breast cancer. Scientists have known for years that the most common breast cancer genes are BRCA1 AND BRCA2, but there are many more than those two genes that scientists now much cope with. Another aspect of the focus is on whether or not to tell a woman that she has genes that might lead to breast cancer; the ethical questions are serious and this is complicated by the fact that ovarian cancer and breast cancer "share genetic risk factors." The overall problem is breast cancer, but within the problem of breast cancer is determining which genes are likely to cause tumors and which are present but do not necessarily lead to breast cancer. The identification of BRCA1 and BRCA2 was thought to hold the keys to identifying those women who had those genes as possible breast cancer victims. But with the "rapid expansion of….

Works Cited

Kean, S. (2014). The 'Other' Breast Cancer Genes. Science, Vol. 343. Retrieved April 7, 2014,

from  http://www.sciencemag.org .

Women's Issues Breast Cancer Awareness

Screening for breast cancer before there are symptoms is very important. Screening helps doctors find and treat cancer in its early stages. Treatment is more likely to be successful when the cancer is detected early. A doctor may suggest any of the following screening tests for breast cancer: screening mammogram, clinical breast exam, beast self-exam (Stoppler, 2009). Mammograms can often show a breast lump before it can even be felt. A mammogram is a picture of the breast that is made with an x-ray. It can also show a cluster of tiny deposits of calcium. These deposits are known as micro calcifications. Lumps can be from cancer, precancerous cells, or a host of other conditions. Further tests may be needed to find out if abnormal cells are present. Women in their 40s and older should have mammograms every 1 to 2 years (Stoppler, 2009). During a clinical breast exam the health….

Cancer Gap Between Whites, Blacks May Be Biological in Part. (2009). Retrieved August 11,

2009, from  http://healthday.com/Article.asp?AID=628785 

Carcinogen Found in KFC's New Grilled Chicken. (2009). Retrieved August 13, 2009, from News and Media Center Web site:  http://www.pcrm.org/news/release090521.html 

National Breast Cancer Awareness Month. (2008). Retrieved August 11, 2009, from American

Life Changing Event That Shaped

Still, getting the right kind of care, at the right time, is often a struggle for patients. My friend passed away from her illness, but her experience opened my eyes to the need to mesh the personal needs of the patient with more effective diagnostic and treatment solutions. I had always wanted to embark upon a financial career, but now I knew what type of entrepreneurship I wished to devote my life to -- biotechnology. Early detection must become a vital component of the war on cancer. Improving screening as well as the quality of treatment, pharmaceuticals, and care are critical components of the emerging 21st century heath care paradigm. Finding a way to financially contain costs, dispense care in a comprehensive and ethical fashion, and creating an effective strategy of prevention will all become the focus of the business of medicine. By becoming part of this graduate program, I….

quantitative research

infer an answer to a particular section, then you must so state and JUSTIFY your statement. DO NOT LEAVE ANY SECTION BLANK. Caution: Do not provide a "Yes" or "no" answer without an EXPLANATION. YOU MUST JUSTIFY ALL YOUR RESPONSES ALL responses must be written in YOUR OWN WORDS. Do NOT use quotes. Morike Adekemi Full and Complete Reference for the Article: Hagan, Teresa L, BSN, RN., B.A., & Donovan, Heidi M, Phd., R.N. (2013). Ovarian cancer survivor's experiences of self-advocacy: A focus group study. Oncology Nursing Forum, 40(2), 140-7. Retrieved from http://searchproquest.com/docview/1325739253?accountid-35812 You must submit the full article in PDF form. Critiques submitted without the PDF will not be accepted. Problem What is the problem the study was conducted to address? (1) Response: The problem this study was conducted to address was self-advocacy in clinical research as well as practice. Despite self-advocacy being cited as a trait desirable among patients, not much explanation or description of this concept is….

Retype Title Here There Are Several Fundamental

etype Title Here There are several fundamental and very important differences between normal cells and cancerous cells. One of these differences has to do with structure. In normal living cells DNA in genes and chromosomes go about their function in a routine and normal manner. Cancerous cells do not function in a normal manner, they develop an abnormal DNA and gene structure and while at the same time developing an abnormal number of chromosomes (Kolata 812). The human body relies on cells for the production and sustainment of energy. In terms of Energy supplementation to the body cancerous cell and normal cell function very differently. Normal cells derive up to 70% percent of their energy from a system known as the Krebs cycle. Cancerous are different in that they have a defective Krebs cycle, they receive very little or no energy from this. Normal cells derive about 20% of their energy from….

Cell Reproduction. (n.d.). Retrieved February 23, 2011, from  http://www.mhhe.com/biosci/genbio/virtual_labs/BL_23/BL_23.html 

Hardman, A.E., & Stensel, D.J. (2009). Physical activity and health the evidence explained. London: Routledge.

Hong, W.K., & Bast, R.C. (2009). Holland Frei Cancer Medicine Volume 8. (2nd ed., Vol. 8). Hartford, Conn.: PHPM-U.S..

Kolata, G.B. (1975). A Major Difference Between Normal Cells and Cancer Cells. The Science Journal, 188(4190), 819-822. Retrieved February 15, 2011.

Causes of a Missed Period beyond Normal Pregnancy

Case Study: JuanitaPatient Information: Juanita Morales is a 47-year-old G5P5LC6 Hispanic female. She presents with symptoms of lower abdominal cramping, urinary leakage, and cessation of menses for 8-12 months. She is well developed and well nourished but obese (BMI 45.89). She has a negative social history for alcohol, tobacco, and recreational drugs. Her last medical exam was several years ago.SubjectiveCC (chief complaint): Lower abdominal cramping and urinary leakage, along with fatigue, for the past day.HPI: Juanita reports the abdominal cramping started several hours ago, is sharp, intermittent, and is increasing in frequency and intensity. She tried Motrin but it provided no relief. Her menses ceased 8-12 months ago. She also reports constipation, increased gas over the past several months, and a possible vaginal spotting several days ago.Current Medications: None reported.Allergies: No known drug allergies.PMH: No past medical or surgical history reported.Soc Hx: Negative for alcohol, tobacco, and recreational drugs.Fam Hx:….

ReferencesAhmad, A., Kumar, M., Bhoi, N. R., Badruddeen, Akhtar, J., Khan, M. I., ... & Ahmad, M. (2023). Diagnosis and management of uterine fibroids: current trends and future strategies. Journal of Basic and Clinical Physiology and Pharmacology, 34(3), 291-310.Dubbewar, A., Srivastava, A., Hiremath, R. N., Ghodke, S., Chourey, N., & Sreenivas, A. (2022). A rare case of spontaneous heterotopic pregnancy with intrauterine gestational trophoblastic neoplasia and tubal ectopic pregnancy at a remote secondary care hospital. Journal of Family Medicine and Primary Care, 11(7), 3996-3998.Martin, M. L., Halling, K., Eek, D., & Reaney, M. (2020). “Lower abdominal pains, as if I was being squeezed… in a clamp”: A Qualitative Analysis of Symptoms, Patient-Perceived Side Effects and Impacts of Ovarian Cancer. The Patient-Patient-Centered Outcomes Research, 13, 189-200.Vitale, A. M., & Lockwood, G. M. (2020). Urine Microscopy: The Burning Truth–White Blood Cells in the Urine. Urine Tests: A Case-Based Guide to Clinical Evaluation and Application, 143-166.

Can you assist me in formulating a thesis on the benefits of breastfeeding?

Thesis Statement: Breastfeeding offers substantial benefits for both mothers and infants, promoting optimal health outcomes and fostering a unique bond between them. Its advantages range from providing essential nutrients to reducing the risk of diseases and enhancing cognitive development in infants, while also providing health benefits and convenience for mothers. Introduction: The practice of breastfeeding has been recognized as a fundamental aspect of parenting, providing infants with the optimal nutrition they need to thrive. This thesis delves into the multitude of benefits breastfeeding offers to both mothers and their infants, highlighting the positive impact it can have on health, development, and emotional....

A mutation of the gene causing colorectal cancer or epithelial ovarian cancer are major risk factors for ovarian cancer, and genetic testing within the laboratory can identify most…

These include bloating, abdominal or pelvic pain, frequent and/or urgent urination, and difficulty eating because one feels very full very quickly (MedicineNet, 2009). However, these were only agreed…

Education - Mathematics

usiness Research Terms and Concepts KNOWING THE DIFFERENCES Understanding Research Terms and Concepts Quantitative Research Methods and Instruments Quantitative research tests hypotheses from theories or approximates the magnitude of a particular phenomenon (Eau…

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Revolutionizing ovarian cancer treatment with adaptive PARP inhibitor therapy

Innovative study reveals dose modulation as key to reducing toxicity and combating resistance.

Ovarian cancer, often diagnosed at an advanced stage, presents significant treatment challenges because patients tend to develop resistance to conventional therapies quickly. Despite aggressive treatment, recurrence rates remain high, and managing this disease effectively requires innovative approaches. Poly-adenosine ribose polymerase (PARP) inhibitors have emerged as a treatment option, targeting specific DNA repair mechanisms in cancer cells. However, their use is often limited by toxicity and emerging drug resistance.

A new study led by researchers at Moffitt Cancer Center introduces an adaptive therapy approach that could optimize PARP inhibitor maintenance therapy, offering a more personalized and potentially less toxic treatment option for patients. Their work is featured as the cover article of the June 19 issue of Cell Systems .

PARP inhibitors are a targeted therapy that block a protein that helps repair damaged DNA. This can keep cancer cells from repairing themselves once they've been damaged by chemotherapy, resulting in cancer cell death. Despite their effectiveness, traditional dosing methods of administering the maximum tolerated dose often result in severe side effects and dose reductions, compromising treatment efficacy.

Moffitt researchers utilized mathematical modeling and in vitro experiments to compare adaptive dosing strategies. They developed a model to test various adaptive schedules and found that dose modulation based on tumor response was superior to skipping doses.

"Adaptive therapy tailors treatment to the tumor's dynamics, allowing us to adjust drug levels to match a patient's specific disease characteristics," said Alexander Anderson, Ph.D., study author and chair of the Integrated Mathematical Oncology Department at Moffitt. "Our findings suggest that modulation, rather than skipping doses, can halve the amount of drug used while maintaining its effectiveness. This approach reduces toxicity and can potentially delay the development of resistance."

The team conducted time-lapse microscopy to observe ovarian cancer cell populations under different treatment schedules. Their model revealed that continuous dose modulation effectively managed the tumor using significantly less medication than traditional methods. In vivo experiments confirmed these results, demonstrating the practical viability of the adaptive approach. While the results are promising, the research continues to validate and refine adaptive therapy strategies.

"A mathematical modeler by training, this project gave me the unique opportunity to conduct my own in vitro experiments to calibrate and test my models. Not only was this a fun and rewarding experience, but it demonstrated to me the power of closely integrating theory and experiments," said Maximilian Strobl, Ph.D., lead author who conducted this work while pursuing a doctorate and postdoc at Moffitt. "I believe such an iterative and interdisciplinary approach will be crucial in developing more effective ways to schedule cancer treatment."

Their work was supported by the National Cancer Institute (U01CA23282, U01CA261841, R01CA249016, R01CA272601) and the Moffitt Center of Excellence for Evolutionary Therapy.

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Materials provided by H. Lee Moffitt Cancer Center & Research Institute . Note: Content may be edited for style and length.

Journal Reference :

• Maximilian A.R. Strobl, Alexandra L. Martin, Jeffrey West, Jill Gallaher, Mark Robertson-Tessi, Robert Gatenby, Robert Wenham, Philip K. Maini, Mehdi Damaghi, Alexander R.A. Anderson. To modulate or to skip: De-escalating PARP inhibitor maintenance therapy in ovarian cancer using adaptive therapy . Cell Systems , 2024; 15 (6): 510 DOI: 10.1016/j.cels.2024.04.003

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Does Kris Jenner Have Cancer? Her Health Explained After Doctors Found a Tumor

During a season 5 episode of 'The Kardashians,' Kris revealed that her doctors discovered a tumor. See all updates about her health, here.

Kris Jenner ‘s health became a concern among fans after she revealed her doctors discovered a tumor in her ovary. During a season 5 episode of The Kardashians , the 68-year-old momager emotionally told her children that she had to undergo a procedure. Now, fans are wondering if Kris has a form of cancer.

Learn everything we know about Kris’ health, below.

What Happened to Kris Jenner?

During episode 7 of season 5, Kris tearfully told her children that her doctor found a tumor.

“I wanted to tell you guys something. I went to the doctor and had my scan,” she said before tearing up. “They found, and this just makes me really emotional but, they found a cyst and a little tumor on my ovary.”

The discovery was difficult for the reality TV personality, as she noted that her health changes are part of aging. “It’s a whole chapter that’s just closed,” she said.

Does Kris Jenner Have Cancer?

While speaking with her daughters Kim , Khloé and Kendall  during the episode, Kris explained that she needed to have her ovaries “taken out.”

“Dr A said I’ve gotta have my ovaries taken out, and I’m emotional about it because they came in handy with you guys,” Kris said. “That’s where all my kids were conceived and that’s where they were grown, in my tummy. So, this is a very sacred place to me.”

After Khloé called Kourtney to share the news, the Lemme founder reflected on the emotional revelation.

“I totally understand how my mom is feeling because I would feel the same way,” Kourtney explained. “It’s your womanly power and it doesn’t mean that it’s taking away who she is or what she’s experienced, but I would feel this sentimental feeling of what it’s created.”

Kris didn’t clarify whether or not the tumor discovery meant a cancer diagnosis. But the momager insisted that she’s “gonna be fine” and added, “Listen, if I can get through the hip replacement, I can get through this. I’m not nervous to be put to sleep. I’m not nervous with Dr. A, she’s the best doctor in the world. But then you go to do it and … it’s so real.”

“People often ask me what is the best job I’ve ever had, and I’ve always said: Mom,” the Keeping Up With the Kardashians alum said. “The biggest blessing in my life was being able to give birth to six beautiful kids.”

Kris Has Faced Health Setbacks Before

Previously, Kris revealed that she had to undergo hip replacement surgery during season 2 of The Kardashians . During the 2022 season, viewers learned that she was feeling “excruciating” pain in her hip and decided to get the surgery. As a result, the reality TV star seemingly adjusted quickly.

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Committee on the State of the Science in Ovarian Cancer Research; Board on Health Care Services; Institute of Medicine; National Academies of Sciences, Engineering, and Medicine. Ovarian Cancers: Evolving Paradigms in Research and Care. Washington (DC): National Academies Press (US); 2016 Apr 25.

Ovarian Cancers: Evolving Paradigms in Research and Care.

• Hardcopy Version at National Academies Press

1 Introduction and Background

Although recent years have seen many promising advances in cancer research, there remain surprising gaps in the fundamental knowledge about and understanding of ovarian cancer. Researchers now know that ovarian cancer, like many other types of cancer, should not be thought of as a single disease; instead, several distinct subtypes exist with different origins, different risk factors, different genetic mutations, different biological behaviors, and different prognoses, and much remains to be learned about them. For example, researchers do not have definitive knowledge of exactly where these various ovarian cancers originate and how they develop. Such unanswered questions have impeded progress in the prevention, early detection, treatment, and management of ovarian cancers. In particular, the failure to achieve major reductions in ovarian cancer morbidity and mortality during the past several decades is likely due to several factors, including

• A lack of research focusing on specific disease subtypes;
• An incomplete understanding of genetic and nongenetic risk factors;
• An inability to develop and validate effective screening and early detection tools;
• Inconsistency in the delivery of the standard of care;
• Limited evidence-based personalized medicine approaches tailored to the disease subtypes and other tumor characteristics; and
• Limited attention paid to research on survivorship issues, including supportive care with long-term management of active disease.

The symptoms of ovarian cancers can be nonspecific and are often not seen as indicating a serious illness by women or their health care providers until the symptoms worsen, at which point the cancer may be widespread and difficult to cure. The fact that these cancers are not diagnosed in many women until they are at an advanced stage is a major factor contributing to the high mortality rate for ovarian cancer, especially for women with high-grade serous carcinoma (HGSC)—the most common and lethal subtype. Indeed, roughly two-thirds of women with ovarian cancer are diagnosed with an advanced-stage cancer or with a cancer that has not been definitively staged, and the 5-year survival rate for these women is less than 30 percent ( Howlader et al., 2015 ). Although many ovarian cancers respond well to initial treatment, including the surgical removal of grossly visible tumor (cytoreduction) and chemotherapy, the vast majority of the tumors recur. Recurrent ovarian cancers may again respond to further treatment, but virtually all of them will ultimately become resistant to current drug therapies.

Finally, less emphasis has been placed on research that focuses on how to improve therapeutic interventions by subtype or on how to reduce the morbidity of ovarian cancers. Little emphasis has been placed on understanding survivorship issues and the supportive care needs of women with ovarian cancer, including management of the physical side effects of treatment (including both initial and chronic, ongoing therapies) and addressing the psychosocial effects of diagnosis and treatment. The lasting impact of a diagnosis of ovarian cancer and its related treatment can be significant both for the women who experience recurrent disease and for the women who experience long (or indefinite) periods of remission. This report gives an overview of the state of the science in ovarian cancer research, highlights the major gaps in knowledge in that field, and provides recommendations that might help reduce the incidence of and morbidity and mortality from ovarian cancers by focusing on promising research themes and technologies that could advance risk prediction, early detection, comprehensive care, and cure.

• STUDY CHARGE AND APPROACH

In spite of their high mortality rates, ovarian cancers often do not receive as much attention as other cancers. In part, this is because ovarian cancers are relatively uncommon. Furthermore, ovarian cancer has been called a “silent killer” because researchers once believed that there were no perceptible symptoms in the earlier stages of the disease ( Goff, 2012 ). However, more recent research has shown that most women diagnosed with ovarian cancer report symptoms such as bloating, pelvic or abdominal pain, and urinary symptoms, and many women recall having these symptoms for an extended period of time before diagnosis ( Goff et al., 2000 , 2004 ). Often, due to the nonspecific nature of ovarian cancer symptoms, patients and physicians do not recognize these early symptoms as indicative of ovarian cancer ( Gajjar et al., 2012 ; Jones et al., 2010 ; Lockwood-Rayermann et al., 2009 ).

In this context, in 2006 the U.S. Congress passed the Gynecologic Cancer Education and Awareness Act of 2005, 1 which amended the Public Health Service Act (42 U.S.C. 247b-17) to direct the secretary of the U.S. Department of Health and Human Services to launch a campaign to “increase the awareness and knowledge of health care providers and women with respect to gynecologic cancers.” The law is commonly known as Johanna's Law in memory of Johanna Silver Gordon, a public school teacher from Michigan who died from late-stage ovarian cancer ( Twombly, 2007 ). The law was reauthorized in 2010, 2 and, as part of the Consolidated Appropriations Act of 2014, Congress directed the Centers for Disease Control and Prevention (CDC) to use funds from Johanna's Law to perform a review of the state of the science in ovarian cancer. 3

Study Charge

In the fall of 2014, with support from the CDC, the Institute of Medicine (IOM) formed the Committee on the State of the Science in Ovarian Cancer Research to examine and summarize the state of the science in ovarian cancer research, to identify key gaps in the evidence base and challenges to addressing those gaps, and to consider opportunities for advancing ovarian cancer research (see Box 1-1 ). The committee determined that the best way to facilitate progress in reducing morbidity and mortality would be to identify the research gaps that were most salient and that, if addressed, could affect the greatest number of women.

Statement of Task.

The committee was also asked to consider ways to translate and disseminate new findings and to communicate these findings to all stakeholders. This report, therefore, not only describes evidence-based approaches to translation and dissemination, but it also suggests strategies for communicating those approaches.

The committee emphasizes that its charge was to focus on research in ovarian cancer and, particularly, to focus on the gaps in the evidence base that, if addressed, would have the greatest impact on the lives of women diagnosed with or at risk for ovarian cancer. The committee did not explore issues affecting the care of women with ovarian cancer (e.g., health insurance coverage and policy issues) in depth. For example, while the regulatory process for drug approval is interconnected with the clinical trial enterprise (e.g., the design of clinical trials may determine what data are gathered and, in turn, affect the approval process), a full examination of issues related to the approval of new drugs was beyond the scope of this report. Furthermore, it was outside the scope of this report to fully evaluate specific research programs in ovarian cancer. In addition, this report does not offer an exhaustive cataloguing of every actor engaged in ovarian cancer research, nor does it detail every effort made by stakeholders to engage in dissemination and implementation efforts. Rather, the examples given in this report are meant to highlight the efforts being made, recognizing there are many other similar efforts.

Finally, the committee focused as much as possible on the research gaps and the challenges to addressing those gaps that are unique to ovarian cancer. However, those research gaps and challenges that are common to all types of cancer research, or even to all health care research, are described as appropriate. For example, while the clinical trials system is extremely important to the ovarian cancer research enterprise, many of the outstanding questions and concerns related to the clinical trials system are shared with all types of cancer research and could not be explored or discussed in detail. Therefore, the committee turned to previous IOM reports specific to the clinical trials system in general for guidance, and then considered aspects of the system that are particularly relevant for ovarian cancer research.

Study Approach

The study committee included 15 members with expertise in ovarian cancer, gynecologic oncology, gynecologic pathology, gynecologic surgery, molecular biology, cancer genetics and genomics, genetic counseling, cancer epidemiology, immunology, biostatistics, bioethics, advocacy, survivorship, and health communication. (See Appendix E for biographies of the committee members.)

A variety of sources informed the committee's work. The committee met in person four times, and during two of those meetings it held public sessions to obtain input from a broad range of relevant stakeholders. In addition, the committee conducted extensive literature reviews, reached out to a variety of public and private stakeholders, and commissioned one paper.

The committee encountered a number of challenges. In some cases, it found itself limited by what was available in the published literature. At other times, it was challenged by the use of different methodologies for the classification of ovarian cancers in the research literature. For instance, many studies in the literature consolidate all types of ovarian cancer instead of studying and reporting them by subtype. In its review of the evidence, the committee discerns, where possible, whether the reported findings apply to ovarian cancers as a whole or to particular subtypes. One other major challenge to reviewing and summarizing the evidence base on ovarian cancer, particularly in summarizing the epidemiology by subtype, was the way that the grading, classification, and nomenclature for ovarian cancers have varied over the years.

In order to guide its deliberative process, the committee chose to make recommendations about research gaps based on the continuum of cancer care (see Figure 1-1 ). The committee focused on cross-cutting research areas critical to each phase of the continuum: the basic biology of ovarian cancers, innovative clinical trial design, intervention development, methods to reduce practice-related disparities, and supportive care research and practice. Finally, the committee considered evidence and strategies for the dissemination and implementation of knowledge across all of these domains.

Framework for research in ovarian cancer. NOTE: Colored figures represent phases of the ovarian cancer care continuum where research can be focused. Black boxes indicate critical areas of ongoing cross-cutting research that span these phases.

• DEFINITIONS OF KEY TERMS

This section provides definitions of several key terms that are relevant to this report, and also provides an explanation of how the committee selected terms for consistency throughout the report. A glossary including more terms is provided in Appendix B , and a list of key acronyms is included in Appendix A .

Target Population

This report is concerned with women with ovarian cancers. However, the committee recognizes that there is a small subpopulation of transgender men who may be at risk for ovarian cancers, particularly due to the use of testosterone therapy ( Dizon et al., 2006 ; Hage et al., 2000 ).

Basic Cancer Terminology

The terms “cancer,” “carcinoma,” and “tumor” can be confused or interchanged at times. Cancer is “a term for diseases in which abnormal cells divide without control and can invade nearby tissues,” while a tumor (which can be cancerous or noncancerous) is “an abnormal mass of tissue that results when cells divide more than they should or do not die when they should” ( NCI, 2015d ). Carcinomas are cancers that “begin in the skin or in tissues that line or cover internal organs” (i.e., arising from epithelial cells) ( NCI, 2015d ). As was noted previously, this report focuses on ovarian carcinomas, because they are the most common and most lethal of the ovarian cancer subtypes.

While the committee endeavored to focus on carcinomas wherever possible, there were times when that was not possible, and the terms “cancer” and “tumor” are used when appropriate. For example, many studies are based on ovarian cancers collectively and do not analyze data based on the subtypes. The committee also uses the term “tumor” when discussing the physical mass itself. Finally, although the term “ovarian cancer” technically represents an array of disease subtypes, the committee refers to the disease in the plural form (i.e., “ovarian cancers”) whenever appropriate in order to emphasize the heterogeneity of the disease and all its subtypes.

When ovarian cancer reappears in a woman, it is usually referred to as “relapsed” or “recurrent” disease. The National Cancer Institute (NCI) defines cancer recurrence as “cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body” ( NCI, 2015d ). Noting that a cancer that has recurred is also called “relapsed cancer,” the NCI defines relapse as “the return of a disease or the signs and symptoms of a disease after a period of improvement.” In this report, for consistency the committee uses only the terms “recurrent” or “recurrence”—and not “relapsed” or “relapse”—but it recognizes that there may be subtle differences, preferences, or interpretations in the use of the two terms.

• DEFINING AND CLASSIFYING OVARIAN CANCERS

“Ovarian cancer” is a generic term that can be used for any cancer involving the ovaries. The ovaries are composed of several different cell types, including the germ cells, specialized gonadal stromal cells (e.g., granulosa cells, theca cells, Leydig cells, and fibroblasts), and epithelial cells; ovarian cancers can arise from any of these cell types. Ovarian cancers with epithelial differentiation (carcinomas) account for more than 85 percent of ovarian cancers and are responsible for most ovarian cancer–related deaths ( Berek and Bast, 2003 ; Braicu et al., 2011 ; SEER Program, 2015 ; Seidman et al., 2004 ). Consequently, this report will focus on the biology of ovarian carcinomas, while recognizing that although other, less common types of ovarian malignancies do exist, they are responsible for a smaller fraction of ovarian cancer–related deaths.

As with ovarian cancers in general, ovarian carcinomas are quite heterogeneous and come in a variety of different tumor types (see Figure 1-2 ). The major ovarian carcinoma subtypes are named according to how closely the tumor cells resemble normal cells lining different organs in the female genitourinary tract. Specifically, serous, endometrioid, and a subset of mucinous carcinomas exhibit morphological features that are similar to normal epithelial cells in the fallopian tube, endometrium, and endocervix, respectively. Furthermore, clear cell carcinomas resemble cells seen in the gestational endometrium ( Scully et al., 1999 ).

Percentage of cases by major ovarian carcinoma subtype. NOTE: Other* refers to mixed or transitional carcinomas where it is not possible to categorize to a single subtype. SOURCES: Gilks et al., 2008; Seidman et al., 2003, 2004.

Over the past several years, researchers have developed a streamlined classification scheme in which the majority of ovarian carcinomas can be divided into five types:

Endometrioid carcinoma (EC),

Clear cell carcinoma (CCC),

Low-grade serous carcinoma (LGSC), and

Mucinous carcinoma (MC) ( Gurung et al., 2013 ; Kalloger et al., 2011 ).

Some researchers have offered an even simpler classification with a scheme in which ovarian carcinomas are divided into Type I and Type II tumors based on shared features ( Shih and Kurman, 2004 ). In this scheme, Type I carcinomas are low-grade, relatively unaggressive, and genetically stable tumors that often arise from recognizable precursor lesions such as endometriosis or benign tumors and frequently harbor somatic mutations that deregulate specific cell signaling pathways or chromatin remodeling complexes. ECs, CCCs, MCs, and LGSCs are considered Type I tumors and are often characterized by KRAS , BRAF , or PTEN mutations. Type II carcinomas are high-grade, biologically aggressive tumors from their inception, with a propensity for metastasis from small, even microscopic, primary lesions. HGSCs represent the majority of Type II tumors and are characterized by the mutation of TP53 and frequent mutations of genes (e.g., BRCA1 and BRCA2 ) that lead to homologous recombination defects ( Pennington et al., 2014 ).

Because the data collected thus far provide compelling evidence that each of the various Type I tumors has distinct biological and molecular features, these tumors will be referred to by their specific histologic type throughout the remainder of this report. However, the Type I and Type II terminology will be used where necessary, most often in referring to studies conducted using this classification scheme. Furthermore, because the majority of ovarian carcinomas are HGSCs, and HGSCs are the subtype with the worst prognosis, this report will primarily focus on this subtype. When referring to historical or large-scale epidemiologic studies of ovarian cancer for which the tumor subtypes were not specified, readers can reasonably assume that most of the tumors were HGSCs.

After being classified by subtype, tumors are usually also assigned a grade, based on how closely the tumor cells resemble their normal counterparts. Both two-grade and three-grade systems have been applied in various situations; in both types of systems, the lower-grade tumors more closely resemble normal cells than the higher-grade tumors ( Malpica et al., 2004 ; Silverberg, 2000 ).

OVARIAN CANCER PATTERNS AND DEMOGRAPHICS 4

Although ovarian cancer is relatively rare, it is one of the deadliest cancers. It was estimated that more than 21,000 women in the United States would receive a diagnosis of an ovarian cancer in the year 2015 5 ( Howlader et al., 2015 ). This represents almost 12 new cases for every 100,000 women and 2.6 percent of all new cancer cases in women in the United States. Nearly 200,000 women in the United States are living with ovarian cancer in any given year, and approximately 1.3 percent of all American women will be diagnosed with ovarian cancer at some point in their lives, which qualifies ovarian cancer as a rare disease as defined by the National Institutes of Health (NIH) Genetic and Rare Diseases Information Center ( NIH, 2015a ). Still, according to estimates, more than 14,000 American women will have died from ovarian cancer in 2015, which corresponds to approximately 7.7 deaths per 100,000 women and 5.1 percent of all cancer deaths among American women ( ACS, 2015 ; Howlader et al., 2015 ). Despite its relatively low incidence, ovarian cancer is the fifth leading cause of cancer deaths among U.S. women and the eighth leading cause of women's cancer deaths worldwide ( Ferlay et al., 2015 ; Howlader et al., 2015 ). By comparison, breast cancer is more common—among American women the estimated number of new cases of breast cancer each year is 10 times the number of new cases of ovarian cancer—but ovarian cancer is more deadly, with a death-to-incidence ratio that is more than three times higher than for breast cancer ( Howlader et al., 2015 ) (see Figure 1-3 ).

The ratio between the death and incidence rates for ovarian, breast, endometrial, and cervical cancers per 100,000 women in the United States, 2008–2012. SOURCE: Howlader et al., 2015.

The survival rate for ovarian cancer is quite low. For 2005 to 2011, the 5-year survival rate in the United States was just 45.6 percent. By contrast, the 5-year survival rate in the United States for the same period was nearly 90 percent for breast cancer, more than 80 percent for endometrial cancer, and nearly 70 percent for cervical cancer. However, given the typical course of initial remission and subsequent recurrence for women with ovarian cancer, the 5-year survival metric may not reflect the overall disease course. At advanced stages, MCs and CCCs in particular have poorer prognoses and survival rates than other carcinoma subtypes ( Mackay et al., 2010 ).

The incidence of ovarian cancer has declined slightly since the mid-1970s, when the incidence was approximately 16 new cases per 100,000 women ( Howlader et al., 2015 ). Mortality from ovarian cancer has also declined—from 9.8 deaths per 100,000 women in 1975 to 7.4 deaths per 100,000 women in 2012. However, the decline in mortality is relatively small when compared to reductions in death rates achieved for most other female gynecological cancers and for breast cancer in women. For example, the death rate from breast cancer fell by one-third between 1975 and 2012, from 31.4 deaths per 100,000 women to 21.3 deaths per 100,000, and the death rate from cervical cancer dropped by more than half during that same period, from 5.6 deaths per 100,000 women to 2.3 deaths per 100,000.

Among women who were diagnosed with ovarian cancer between 1975 and 1977, only 36 percent lived 5 years or more, while nearly half (46 percent) of women diagnosed with ovarian cancer between 2005 and 2007 lived at least 5 years beyond their diagnosis ( Howlader et al., 2015 ). However, that improvement in survival rates was driven primarily by improvements in survival among white women; survival rates decreased (from 42 to 36 percent) over the same period for black women ( ACS, 2015 ; also see section Race and Ethnicity later in this chapter).

Stage Distribution

Ovarian cancer's high mortality and low survival rates can be attributed in part to the fact that it is rarely diagnosed at an early stage. Indeed, 60 percent of women are diagnosed with advanced disease, when the cancer has already spread beyond the ovary to distant organs or lymph nodes ( Howlader et al., 2015 ). In comparison, as seen in Figure 1-4 , other female cancers are more commonly diagnosed during the localized or regional stages.

Distribution (percentage) of stage of diagnosis for cancers of the breast, endometrium, cervix, and ovary among U.S. women, 2005–2011. SOURCE: Howlader et al., 2015.

The relatively late stage of diagnosis for ovarian cancer is particularly important because survival is highly correlated with the stage at diagnosis (see Figure 1-5 ). While the 5-year survival rate is 45.6 percent overall, it is substantially higher for women diagnosed while the cancer is still at the localized stage (92.1 percent) or the regional stage (73.2 percent), and it is substantially lower for women diagnosed at the distant stage (28.3 percent) ( ACS, 2015 ; Howlader et al., 2015 ). Survival is lowest among women who receive an unstaged ovarian cancer diagnosis (22.9 percent).

Five-year relative survival (percentage) from ovarian cancer by stage at diagnosis among U.S. women, 2005–2011. SOURCE: Howlader et al., 2015.

White and black women show similar patterns of stage distribution (see Figure 1-6 ). However, there is a difference in stage of diagnosis in women of different ages, with women younger than age 65 tending to be diagnosed at earlier stages than women older than age 65 (see Figure 1-7 ).

Stage distribution (percentage of cases) at diagnosis among white and black U.S. women diagnosed with ovarian cancer, 2003–2009. SOURCE: Howlader et al., 2015.

Stage distribution (percentage of cases) at diagnosis among women diagnosed with ovarian cancer by age, 2003–2009. SOURCE: Howlader et al., 2015.

Ovarian cancer incidence increases with age, with a sharp increase in the rate beginning in the mid-40s (see Figure 1-8 ). From 2008 to 2012, nearly 88 percent of all new cases of ovarian cancer occurred among women ages 45 and older, with 69 percent of cases among women ages 55 and older, and the average age at diagnosis was 63 years. A half-century ago, most cases occurred among women between the ages of 35 and 63, and the average age at diagnosis was 48.5 years ( Munnell, 1952 ).While the age-adjusted incidence rate for ovarian cancer among all women is nearly 12 cases per 100,000 women, the rate varies sharply with age, with women younger than age 65 having an incidence rate of 7.5 cases per 100,000 women while women 65 years old and older have an incidence rate of more than 42 cases per 100,000 women ( Howlader et al., 2015 ).

Age-adjusted incidence of ovarian cancer per 100,000 women in the United States by age group. SOURCE: SEER Program, 2015.

Mortality rates also increase sharply with age. The death rate for women aged 65 and older is approximately 13 times that of women less than age 65 (see Figure 1-9 ). Furthermore, while mortality rates have declined overall in the past 40 years, most of this decline is attributable to decreases in mortality among women diagnosed with ovarian cancer less than age 65 ( ACS, 2015 ; Howlader et al., 2015 ).

Trends in age-adjusted death rates from ovarian cancer per 100,000 women in the United States by age group, 1975–2012. SOURCE: Howlader et al., 2015.

Race and Ethnicity

The patterns of ovarian cancer incidence and mortality differ substantially among women of different races and ethnic backgrounds (see Figure 1-10 ). Whites have the highest incidence of ovarian cancer, followed by Hispanics, American Indian/Alaska Natives, blacks, and Asian/ Pacific Islanders ( ACS, 2015 ; Howlader et al., 2015 ; Singh et al., 2014 ). The 5-year survival rate is highest among Asian/Pacific Islanders, followed by Hispanics, whites, American Indian/Alaska Natives, and blacks, while mortality rates are highest among whites, followed by blacks, Hispanics, American Indian/Alaska Natives, and Asian/Pacific Islanders. A particularly dramatic contrast can be seen between black and Asian/Pacific Islander women. While the two groups are similar in having low incidence rates, black women have the second-highest mortality rates and the lowest survival rates, while Asian/Pacific Islanders have the lowest mortality and the highest survival rates. The incidence of ovarian cancer, particularly HGSC, is higher than average in women of Ashkenazi Jewish ancestry, in part because of the higher prevalence of deleterious mutations in cancer-predisposition genes such as BRCA1 and BRCA2 among these women ( ACS, 2015 ; Moslehi et al., 2000 ).

FIGURE 1-10

Age-adjusted ovarian cancer incidence and mortality per 100,000 U.S. women by race and ethnicity, 2008–2012. SOURCE: Howlader et al., 2015.

Furthermore, the variations in the incidence rates of ovarian cancer by race and ethnicity change as women age (see Figure 1-11 ). For example, whites and Asian/Pacific Islanders have similar incidence rates until around age 50, when their incidence rates begin to diverge. White women aged 45–49 have an age-specific incidence rate of 15.1 cases per 100,000, and Asian/Pacific Islanders of the same age group have a very similar rate of 15.5 cases per 100,000. By contrast, white women aged 80–84 have an incidence rate of 50.8 cases per 100,000, while Asian/Pacific Islanders of the same age group have a dramatically lower rate of 30.1 cases per 100,000.

FIGURE 1-11

Age-specific incidence rates of ovarian cancer per 100,000 women in the United States by race/ethnicity and age at diagnosis, 2008–2012. NOTE: Rates for American Indian/Alaska Natives are only displayed for ages 50 through age 69, because the (more...)

Historical trends also show considerable variations by race. Between 2003 and 2012, mortality rates decreased significantly among whites and Hispanics, while declines in mortality among blacks, Asian/Pacific Islanders, and American Indian/Alaskan Natives were not statistically significant ( Howlader et al., 2015 ). Moreover, while survival rates have increased among women overall and among white women since the mid-1970s, survival rates have declined slightly among black women (see Figure 1-12 ). Furthermore, although black women had higher rates of survival compared to white women and to women overall in 1975, by the mid-1980s survival rates had begun to reverse, such that black women now have lower survival rates than white women and women of all races overall even despite gains in survival among blacks in the 1990s ( ACS, 2015 ).

FIGURE 1-12

Trends in 5-year relative survival rates (percentage) for ovarian cancer among U.S. women by race, 1975–2011. SOURCE: Howlader et al., 2015.

In the United States, there are slight geographic variations in ovarian cancer incidence, but these variations are not significant ( Howlader et al., 2015 ; Ries et al., 2007 ). However, the differences in mortality from state to state are significant. In the United States, from 2008 to 2012 the death rate for ovarian cancer was 7.7 deaths per 100,000 women. During that same period, the age-adjusted death rates by state ranged from a low of 5.3 deaths per 100,000 women in Hawaii to a high of 9.0 deaths per 100,000 women in Oregon ( Howlader et al., 2015 ). Despite the wide variation across the states, only Alabama, Oregon, Pennsylvania, and Washington have significantly higher rates, statistically speaking, than the United States as a whole, while only Florida, Hawaii, and Texas have significantly lower rates than the national average.

Ovarian cancer incidence and mortality also vary internationally, with incidence and mortality rates being higher in more developed regions than in less developed regions ( Ferlay et al., 2015 ).

Aside from genetics (e.g., the higher proportion of mutations in cancer-predisposition genes among Ashkenazi Jewish women), the reasons behind the racial and ethnic differences in outcomes are unknown, but they might be explained in part by other variables such as differences in access to health care or the quality of that care ( Baicker et al., 2005 ; IOM, 2003 , 2012 ). Similarly, the reasons behind geographic variation in the demographics of ovarian cancer are unknown, and might be explained by other variables such as race and ethnicity (e.g., the higher proportion of Asian and Pacific Islanders in Hawaii) or differences in access to health care or the quality of that care in different geographic regions ( Baicker et al., 2005 ; IOM, 2003 , 2012 ). (See Chapter 4 for more on access and standards of care for women with ovarian cancer.) Overall, as noted previously, reporting on the demographics and epidemiology of ovarian cancer is challenging because of the fact that most of the data sources aggregate the various subtypes, and even when the data are reported by subtype, differences in the grading, classification, and nomenclature of the subtypes create challenges in summarizing and comparing data.

• THE LANDSCAPE OF STAKEHOLDERS IN OVARIAN CANCER RESEARCH

Many public and private organizations are involved in funding, supporting, and carrying out ovarian cancer research, and they are involved in a variety of ways. The research is sometimes focused on ovarian cancers exclusively, but it sometimes looks at broader populations (e.g., women with gynecologic cancers). A complete cataloguing of every stakeholder in ovarian cancer research and of their individual efforts is beyond the scope of this report. Instead, this section offers an overview of the wide range of stakeholders and highlights the areas of ovarian cancer research that are getting the most attention and the methods used by stakeholders to communicate about new findings in ovarian cancer research.

Federal Stakeholders

While there are a number of different federal stakeholders in ovarian cancer research, the CDC, the U.S. Department of Defense (DoD), and the NIH (and the NCI in particular) are collectively responsible for the majority of the funding for ovarian cancer research at the federal level. The sections below give an overview of the funding levels and focus areas for these agencies. Where possible, the areas of focus are presented in alignment with the Common Scientific Outline (CSO), an international classification system used by cancer researchers to compare research portfolios. The CSO consists of seven broad areas of interest:

Etiology (causes of cancer);

Prevention;

Early detection, diagnosis, and prognosis;

Cancer control, survivorship, and outcomes research; and

Scientific model systems ( DoD, 2015b ).

Centers for Disease Control and Prevention

The CDC conducts and supports studies, often in collaboration with partners, to “develop, implement, evaluate, and promote effective cancer prevention and control practices” ( CDC, 2015 ). In general, the CDC approaches cancer by monitoring cancer demographics (surveillance), by conducting research and evaluation, by partnering with other stakeholders to help translate evidence, and by developing educational materials ( CDC, 2015 ). Most of the CDC's work in ovarian cancer is performed through its Division of Cancer Prevention and Control. 6 Since fiscal year (FY) 2000, the CDC has received about $5 million annually in congressional appropriations to support its Ovarian Cancer Control Initiative. In addition, in 2008 the CDC started receiving funds under Johanna's Law to improve communication with women regarding gynecologic cancers. The CDC's Inside Knowledge 7 campaign works to raise awareness about cervical, ovarian, uterine, vaginal, and vulvar cancers. Between 2010 and 2014, ads produced for the Inside Knowledge campaign were seen or heard around 3.5 million times and were worth a total of $136 million in donated ad value ( CDC, 2014 ).

U.S. Department of Defense

The DoD's Ovarian Cancer Research Program (OCRP) 8 received congressional appropriations from FY 1997 to FY 2014 totaling $236.45 million and received another $20 million in appropriations for FY 2015 ( DoD, 2015a ). Since the inception of the DoD OCRP, more than 130 ovarian cancer survivors have taken part in efforts to establish the OCRP's priorities and research award mechanisms, and they have helped choose the research to be funded. From FY 1997 through FY 2013, the OCRP funded 313 awards in a variety of areas (see Figure 1-13 ). These awards show a focus on biology, treatment, and early detection, diagnosis, and prognosis. OCRP's research priorities include understanding the precursor lesions, microenvironment, and pathogenesis of all types of ovarian cancer; developing and improving the performance and reliability of screening, diagnostic approaches, and treatment; developing or validating models to study initiation and progression; investigating tumor response to therapy; and enhancing the pool of ovarian cancer scientists ( DoD, 2015a ).

FIGURE 1-13

Areas of ovarian cancer research funded by OCRP, FY 1997–2011. SOURCE: DoD, 2015b.

National Institutes of Health

The NCI of the NIH has initiated several activities to advance ovarian cancer research with intramural and extramural funding. In the past, five ovarian cancer–specific specialized programs of research excellence (SPOREs) in the United States conducted ovarian cancer research in early detection, imaging technologies, risk assessment, immunosuppression, and novel therapeutic approaches ( NCI, 2015e ). The NCI currently lists four active SPOREs for ovarian cancer.

The NCI is involved in ovarian cancer research in a variety of other ways. For example, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) is trying to understand the molecular basis of cancer in order to help improve the diagnosis, treatment, and prevention of cancer ( NCI, 2015b ). To accomplish these goals, CPTAC is using the data collected by The Cancer Genome Atlas (TCGA) analysis of ovarian tumors. The NCI has also supported a follow-up of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to analyze the biological material and risk factor information in order to better understand the risks and identify early biomarkers, including biomarkers for ovarian cancers. (See Chapter 3 for more on the PLCO Cancer Screening Trial.)

Overall, the NCI supported $100.6 million in research 9 related to ovarian cancer in FY 2013 while providing $559.2 million for breast cancer research, $63.4 million for cervical cancer research, and $17.8 million for endometrial cancer research ( NCI, 2015g ). However, the research projects listed as being related to ovarian cancer are not necessarily limited to ovarian cancer, and they include studies of multiple cancers (including ovarian cancer) or areas of cross-cutting research related to ovarian cancer. Furthermore, data collected by the DoD 10 through the International Cancer Research Partnership indicates that the funded amount is significantly less when considering only new grants awarded by the NCI each year. Only 52 projects involving ovarian cancer research totaling $33.4 million were started in 2010, 58 new projects totaling $20.4 million in 2011, and 52 new projects totaling $16.3 million in 2012 ( ICRP, 2015 ). Figure 1-14 shows that, like the DoD, the NCI portfolio for ovarian cancer research focuses primarily on treatment, biology, and early detection, diagnosis, and prognosis.

FIGURE 1-14

Areas of ovarian cancer research funded by the NCI. SOURCE: NCI, 2013.

The Office of Cancer Survivorship (OCS), 11 part of the Division of Cancer Control and Population Sciences at the NCI, “works to enhance the quality and length of survival of all persons diagnosed with cancer and to minimize or stabilize adverse effects experienced during cancer survivorship. The office supports research that both examines and addresses the long- and short-term physical, psychological, social, and economic effects of cancer and its treatment among pediatric and adult survivors of cancer and their families” ( NCI, 2014 ).

Figure 1-15 shows the areas of cancer survivorship research expertise at the NCI. As of October 2015, the Division of Cancer Control and Population Sciences had two open funding opportunities for general cancer survivorship research: one focused on the efficacy and impact of care planning, and the other examined the effects of physical activity and weight control interventions on cancer prognosis and survival ( NCI, 2015a ). Neither of these grant opportunities specified a focus on ovarian cancer survivorship.

FIGURE 1-15

Expertise areas for cancer survivorship research at the NCI. SOURCE: NCI, 2015c.

Private Stakeholders

A wide variety of private stakeholders are engaged in ovarian cancer research, including professional societies, advocacy organizations, women's health groups, and disease-specific foundations. In some cases, the organization specifically focuses on ovarian cancer and ovarian cancer research. However, many others focus on cancer or women's health broadly (e.g., the American Cancer Society and the American Congress of Obstetricians and Gynecologists). Overall, private funders of ovarian cancer research tend to focus funding on biology and treatment, with very little funding directed toward the etiology of ovarian cancer or survivorship issues.

Private stakeholders can support young researchers with grant funding; provide training and educational opportunities; encourage collaborative, transdisciplinary efforts; and engage consumers, survivors, and their families. Examples of previous and current efforts by individual private stakeholders include

• The Health, Empowerment, Research, and Awareness Women's Cancer Foundation awarded the Sean Patrick Multidisciplinary Collaborative Grant for cross-disciplinary projects to allow scientists to come together and test ideas that may not be fundable by other agencies ( HERA, 2015 ).
• The Marsha Rivkin Center for Ovarian Cancer Research awards Bridge Funding Awards to researchers who are close to fundable grant scores for the DoD or the NIH but require additional data to ensure a successful resubmission ( Rivkin Center, 2015 ).
• The Ovarian Cancer Research Fund (OCRF) provides funding to researchers at all stages of their careers; OCRF awards include funding for recent graduates, newly independent researchers who are building laboratories, and senior researchers working on collaborative projects ( OCRF, 2015 ).
• The Society of Gynecologic Oncology (SGO) released Pathways to Progress in Women's Cancer in 2011, a research agenda based on discussions of working groups at a 2010 research summit. One working group focused on ovarian cancers, and the report provides short-term, intermediate, and long-term research priorities ( SGO, 2011 ).
• The Honorable Tina Brozman Foundation for Ovarian Cancer Research (also known as Tina's Wish) funds research specifically in the early detection and prevention of ovarian cancer and also supports a consortium to advance such research ( Tina's Wish, 2015 ).

The Role of Advocacy in Ovarian Cancer Research

Advocacy has positively affected ovarian cancer research, public knowledge, and awareness. Many different types of people play the role of advocate—women with ovarian cancer, partners, family members, health care professionals, and activists—and their advocacy efforts range from the individual, patient level to the societal level, but all of these different efforts have had effects on funding efforts, policy change, and the direction of research.

Patients self-advocate by taking active roles in their own care. Researchers have recognized this concept of self-advocacy as an important part of patient-centered care, and it has been described as “a distinct type of advocacy in which an individual or group supports and defends their interests either in the face of a threat or proactively to meet their needs” ( Hagan and Donovan, 2013 , p. 3). However, despite claims that self-advocacy may improve quality of life, health care use, and symptom management, these potential effects have not been adequately studied.

Nurses can serve as advocates for patients by protecting patients' rights, incorporating patients' beliefs and values into their care plans, and respecting the autonomy of the patient to ensure access to quality care ( Temple, 2002 ). Advocacy groups provide education, information, and personal support to patients, family caregivers, and the general public. Many advocacy groups also use lobbying efforts to influence policy, including the direction of research and funding.

Large-scale advocacy efforts have arguably had a great impact on cancer research and funding. In the late 1990s, survivors advocated for wider recognition of early-stage ovarian cancer symptoms. Until that time, physicians and medical textbooks had claimed that women did not experience symptoms until advanced stages of disease ( Twombly, 2007 ). Johanna's Law is considered a victory of advocacy groups' lobbying efforts. Furthermore, Congress has appropriated funds for ovarian cancer research and education programs since FY 1997. The establishment and unified efforts of national advocacy organizations are partially responsible for the significant funding increases in the intervening years ( Temple, 2002 ).

Advocacy groups have also been integral to the advancement of ovarian cancer research through their participation in the design and administration of studies ( Armstrong et al., 2014 ; Holman et al., 2014 ). The scientific literature emphasizes the importance of patient advocates in patient-centered research, citing examples of the collaboration between researchers and patient advocates in research studies ( Armstrong et al., 2014 ; Holman et al., 2014 ; Staton et al., 2008 ).

Several large advocacy groups at the national and international levels focus on ovarian cancer. For example, the Ovarian Cancer National Alliance (OCNA), a national advocacy organization, has among its activities the Survivors Teaching Students: Saving Women's Lives ® program, which is aimed at educating caregivers and medical, nursing, and other professional students about the early signs and symptoms of ovarian cancer. Recently, OCNA spearheaded the formation of the first congressional Ovarian Cancer Caucus with the support of Rosa DeLauro (D-CT) and Sean Duffy (R-WI). The first meeting was held on September 29, 2015, in Washington, DC. The National Ovarian Cancer Coalition (NOCC), another national advocacy organization, funds the Teal Initiative to improve education and awareness. NOCC also supports specific research in ovarian cancer and provides survivor support, primarily through its Faces of Hope program, which is “dedicated to improving the quality of life for women affected by ovarian cancer, as well as providing support for their loved ones and caregivers” ( NOCC, 2014 ). At the international level, the charity Ovarian Cancer Action encourages collaboration among ovarian cancer researchers around the world. Half of its funds go to the Ovarian Cancer Action Research Centre in the United Kingdom, which exclusively supports “research that can be translated into meaningful outcomes for real women in real life” ( Ovarian Cancer Action, 2015 ). In addition, every few years Ovarian Cancer Action hosts an international forum to bring researchers together to share information, inspire collaboration, and develop white papers. In 2011 the forum developed the paper Rethinking Ovarian Cancer: Recommendations for Improving Outcomes , which outlined recommendations for improving outcomes for women with ovarian cancer ( Vaughan et al., 2011 ). A number of other advocacy groups work at the local and national levels to support research in ovarian cancer.

The Role of Consortia and Collaboration in Ovarian Cancer Research

Because of the relative rarity of ovarian cancers, especially when subdivided according to subtypes, collaborative research efforts are necessary in order to collect sufficient data for statistically significant results. Many consortia and multisite studies have evolved to promote the sharing of biospecimens, clinical data, and epidemiologic data in order to ensure sufficient sample sizes in studies. These consortia and collaborations operate at both the national and international levels. Common uses of consortia include carrying out research on the genetic and nongenetic risk factors of developing ovarian cancers, studying mechanisms of disease relapse and resistance, and identifying newer therapies ( AOCS, 2015 ; COGS, 2009 ; NRG Oncology, 2015 ; OCAC, 2015 ; OCTIPS, 2015 ). Furthermore, groups will often team together in coalitions to promote transdisciplinary research and also to promote the translation and dissemination of information. For example, in 2015, OCNA, NOCC, and OCRF provided funding for the Stand Up To Cancer (SU2C) Dream Team for ovarian cancer. This team will bring together experts in DNA repair, translational investigators, and clinicians “to create new programs in discovery, translation, and clinical application, while cross-fertilizing and educating researchers at all levels to enhance collaboration and catalyze translational science” (SU2C, 2015).

Consortia and coalitions have had clear, measureable impacts on the research base for ovarian cancers. For example, as a result of the Collaborative Oncological Gene-environment Study (COGS), 14 new markers for risk of ovarian cancer were identified (only 8 had been known before COGS) ( COGS, 2014 ). Based on the work of this coalition, TCGA researchers completed a detailed analysis of ovarian cancer, which confirmed that mutations in the TP53 gene (which encodes a protein that normally suppresses tumor development) are present in nearly all HGSCs ( Bell et al., 2011 ). The analysis also examined gene expression patterns and identified signatures that correlate with survival outcomes, affirmed four subtypes of HGSCs, and identified dozens of genes that might be targeted by gene therapy ( NIH, 2011 , 2015b ).

NCI's National Clinical Trials Network

In 1955 the NCI established the Clinical Trials Cooperative Group Program. As the science of cancer treatment was evolving, researchers realized that collaborative efforts were necessary to accrue sufficient numbers for clinical trials in order to more rapidly compare the value of new therapies to existing standards of care, particularly for the use of chemotherapy in the treatment of solid tumors ( DiSaia et al., 2006 ; IOM, 2010b ). The work of the cooperative groups led to advances in the treatment of women with ovarian cancer specifically, including a demonstration of the value of adding paclitaxel to cisplatin, confirmation of the value of cytoreductive surgery, and a demonstration of the value of carboplatin for late-stage ovarian cancers ( IOM, 2010b ). The groups have also studied issues related to the quality of life and the prevention of ovarian cancer. Between 1970 and 2005, clinical trials of the Gynecologic Oncology Group (GOG) alone included approximately 35,000 women with ovarian cancer ( DiSaia et al., 2006 ).

In 2014, based in part on the IOM report A National Cancer Clinical Trials System for the 21st Century , the NCI transformed the cooperative group program into the new National Clinical Trials Network ( IOM, 2010b , 2011 , 2013b ; NCI, 2015f ). This reorganization consolidated nine cooperative groups into five new groups:

• The Alliance for Clinical Trials in Oncology;
• The ECOG-ACRIN Cancer Research Group (a merger of two cooperative groups: the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network);
• NRG Oncology (a merger of three cooperative groups: the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the GOG);
• The Southwest Oncology Group; and
• The Children's Oncology Group ( NCI, 2015f ).
• PREVIOUS WORK AT THE INSTITUTE OF MEDICINE

The IOM has a long history of producing reports related to various aspects of cancer care, and many of them are directly relevant to this current study. This section describes some examples of previous IOM work that is related to the work of this committee.

Prevention and Early Detection

In 2005 the IOM report Saving Women's Lives: Strategies for Improving Breast Cancer Detection and Diagnosis ( IOM, 2005 ) recommended the development of tools to identify the women who would benefit most from breast cancer screening based on “individually tailored risk prediction techniques that integrate biologic and other risk factors.” The report also called for the development of tools that “facilitate communication regarding breast cancer risk to the public and to health care providers.” In addition, the report called for more research on breast cancer screening and detection technologies, including research on various aspects of technology adoption (e.g., monitoring the use of technology in clinical practice).

A 2007 IOM report, Cancer Biomarkers , offered recommendations on the methods, tools, and resources needed to discover and develop biomarkers for cancer; guidelines, standards, oversight, and incentives needed for biomarker development; and the methods and processes needed for clinical evaluation and adoption of such biomarkers ( IOM, 2007a ). Specific recommendations from the report included establishing international consortia to generate and share data, supporting high-quality biorepositories of prospectively collected samples, and developing criteria for conditional coverage of new biomarker tests. Subsequently, in 2010, an IOM report, Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease , outlined a framework for the evaluation of biomarkers ( IOM, 2010a ).

In Initial National Priorities for Comparative Effectiveness Research ( IOM, 2009 ), the committee offered two priorities that are relevant to ovarian cancer genetics: “Compare the effectiveness of adding information about new biomarkers (including genetic information) with standard care in motivating behavior change and improving clinical outcomes” and “Compare the effectiveness of genetic and biomarker testing and usual care in preventing and treating breast, colorectal, prostate, lung, and ovarian cancer, and possibly other clinical conditions for which promising biomarkers exist” ( IOM, 2009 , p. 4).

In 2007, the IOM's National Cancer Policy Forum hosted a workshop on cancer-related genetic testing and counseling. According to the published summary of that workshop, participants observed that “genetic testing and counseling are becoming more complex and important for informing patients and families of risks and benefits of certain courses of action, and yet organized expert programs are in short supply. The subject matter involves not only the scientific and clinical aspects but also workforce and reimbursement issues, among others” ( IOM, 2007b )

Clinical Trials

The 2005 IOM report on breast cancer detection called for public health campaigns and for improved information and communication about the value of participation in clinical trials (including the participation of healthy individuals).

A 2010 report, A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program ( IOM, 2010b ), called for the restructuring of the NCI Cooperative Group Program and set four goals:

Improve the speed and efficiency of the design, launch, and conduct of clinical trials (e.g., improve collaboration among stakeholders);

Incorporate innovative science and trial design into cancer clinical trials (e.g., support standardized central biorepositories, develop and evaluate novel trial designs);

Improve the means of prioritization, selection, support, and completion of cancer clinical trials (e.g., develop national unified standards); and

Incentivize the participation of patients and physicians in clinical trials (e.g., develop electronic tools to alert clinicians to available trials for specific patients, encourage eligibility criteria to allow broad participation, cover cost of patient care in trials).

Palliative and End-of-Life Care

Improving Palliative Care for Cancer ( IOM, 2001 ) called for incorporating palliative care into clinical trials. The report also noted that information on palliative and end-of-life care is largely absent from materials developed for the public about cancer treatment, and the committee recommended strategies for disseminating information and improving education about end-of-life care. The report recommended that the NCI require comprehensive cancer centers to carry out research in palliative care and symptom control and that the Health Care Finance Administration (now the Centers for Medicare & Medicaid Services) fund demonstration projects for service delivery and reimbursement that integrate palliative care throughout the course of the disease.

Dying in America ( IOM, 2015 ) noted that palliative care can begin early in the course of treatment, in conjunction with treatment, and can continue throughout the continuum of care. The report further observed that “a palliative approach can offer patients near the end of life and their families the best chance of maintaining the highest possible quality of life for the longest possible time” ( IOM, 2015 , p. 1).

Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis ( IOM, 2013a ) addressed the delivery of cancer care, including palliative and end-of-life care. The study called for providing patients and their families with understandable information about palliative (and other) care and recommended that “the cancer care team should provide patients with end-of-life care consistent with their needs, values, and preferences” ( IOM, 2013a , p. 9).

Communication and Survivorship

From Cancer Patient to Cancer Survivor ( IOM, 2006 ) called for actions to raise awareness about the needs of cancer survivors, including the establishment of cancer survivorship as a distinct phase of cancer care. In 2008, the IOM report Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs ( IOM, 2008 ) recommended that facilitating effective communication between patients and care providers, identifying psychosocial health needs, and engaging and supporting patients in managing their illnesses should all be considered as part of the standard of care. The report emphasized the importance of educating patients and their families and of enabling patients to actively participate in their own care by providing tools and training in how to obtain information, make decisions, solve problems, and communicate more effectively with their health care providers. The report further called for the government to invest in a large-scale demonstration and evaluation of various approaches to the efficient provision of psychosocial health care.

Women's Health Research ( IOM, 2010c ) found that there are many barriers to the translation of research findings in general and that some have aspects that are “peculiar to women.” The committee recommended specific research on how to translate research findings on women's health into clinical practice and public health policies.

Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis ( IOM, 2013a ) called for providing patients and their families with “understandable information on cancer prognosis, treatment benefits and harms, palliative care, psychosocial support, and estimates of the total and out-of-pocket costs of cancer care.” The report further called for the development of decision aids to be made available through print, electronic, and social media; for the formal training of cancer care team members in communication; for the communication of relevant and personalized information at key decision points along the continuum of cancer care; and for consideration of patients' individual needs, values, and preferences when developing a care plan, including end-of-life care. The report also called for the identification and public dissemination of evidence-based information about cancer care practices that are unnecessary or for which the harm may outweigh the benefits.

• OVERVIEW OF THE REPORT

This chapter has provided an overview of the study charge and the committee's approach to its work. It has also provided an introduction to the challenges in ovarian cancer research, to defining and classifying ovarian cancers, to the patterns and demographics of the disease, and to the landscape of stakeholders in ovarian cancer research. The remaining chapters follow the research framework outlined in Figure 1-1 .

Chapter 2 describes the current state of the science in the biology of ovarian cancers, thus providing a foundation for the descriptions of most of the other ovarian cancer research covered in this report. This background includes information about the characteristics of specific ovarian carcinomas, the role of the tumor microenvironment, and experimental model systems.

Chapter 3 builds on this to discuss research on the prevention and early detection of ovarian cancers. On the topic of risk assessment, the chapter includes discussions of a wide range of genetic and nongenetic risk factors for the development of an ovarian cancer, risk-prediction models, and genetic testing. Concerning prevention, both surgical and nonsurgical prevention strategies are discussed. And on the topic of early detection, the chapter has descriptions of various approaches to identifying ovarian cancers earlier, including biomarkers and imaging techniques, and a discussion of the challenges in performing screening in both general and high-risk populations.

Chapter 4 describes the research base for the diagnosis and treatment of women newly diagnosed with ovarian cancer as well as for women with relapsed ovarian cancer. The chapter outlines research on current standards of care and also explores the development of novel therapeutics such as anti-angiogenics, poly ADP ribose polymerase (PARP) inhibitors, and immunotherapy. Later, the chapter discusses issues of clinical trial development and use as they relate specifically to research in ovarian cancer.

Chapter 5 discusses research on survivorship and management issues along the entire care continuum from diagnosis to end of life. Furthermore, women who are at a high risk for developing cancer (sometimes referred to as “previvors”) may have psychosocial needs of their own that should be studied. Overall, research that focuses specifically on survivorship and management issues in ovarian cancer is scarce; it may thus be necessary to apply research from broader studies of survivorship to women with ovarian cancer. The chapter discusses the research base for the unique issues of survivorship and management for women with ovarian cancer and their families, including managing the physical side effects of treatment, addressing unique psychosocial impacts, engaging women in their own self-care, and addressing end-of-life concerns.

Chapter 6 summarizes the findings and conclusions of the previous chapters in order to provide a cohesive set of recommendations for prioritizing research on ovarian cancers in such a way as to have the greatest impact on reducing morbidity and mortality from the disease.

Chapter 7 gives an overview of research on the translation and dissemination of new information to the general public, providers, researchers, policy makers, and others. The chapter reflects on the messages within the previous chapters that are ready to be communicated and identifies potential avenues for communicating these messages.

Finally, the report contains five appendixes. Appendix A contains a list of key acronyms used throughout the report. Appendix B contains a glossary of key terms. Appendix C includes a listing of currently active studies on epithelial ovarian cancer (based on information available through www.ClinicalTrials.gov ) in order to give a sense of where emphasis is being placed in future research. Appendix D lists the agendas of the committee's workshops. Appendix E contains the biographical sketches of the committee members and project staff.

Gynecologic Cancer Education and Awareness Act of 2005, Public Law 475, 109th Cong., 2nd sess. (January 12, 2007).

To reauthorize and enhance Johanna's Law to increase public awareness and knowledge with respect to gynecologic cancers, Public Law 324, 111th Cong., 2nd sess. (December 22, 2010).

Explanatory statement submitted by Mr. Rogers of Kentucky, Chairman of the House Committee on Appropriations regarding the House amendment to the Senate amendment on H.R. 3547, consolidated… , 113th Cong., 2nd sess., Congressional Record 160, no. 9, daily ed. (January 15, 2014):H 1035.

Terminology to describe race and ethnicity reflects the terminology used in the original sources.

Because historical epidemiologic data typically combine the multiple types of ovarian cancer, they are discussed as a single disease in this discussion of epidemiology.

For more information, see http://www ​.cdc.gov/cancer/dcpc/about (accessed July 21, 2015).

For more information, see http://www ​.cdc.gov/cancer/knowledge (accessed September 1, 2015).

For more information, see http://cdmrp ​.army.mil/ocrp (accessed July 21, 2015).

The NCI notes that “the estimated NCI investment is based on funding associated with a broad range of peer-reviewed scientific activities” ( NCI, 2015g ). The NCI research portfolio for ovarian cancer may be found at http: ​//fundedresearch ​.cancer.gov/nciportfolio ​/search/get?site ​=Ovarian+Cancer&fy=PUB2013 (accessed December 2, 2015).

Personal communication, Patricia Modrow, data assembled by the U.S. Department of Defense Ovarian Cancer Research Program, January 16, 2015.

For more information about the OCS, see http: ​//cancercontrol.cancer.gov/ocs (accessed May 15, 2015).

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• Cite this Page Committee on the State of the Science in Ovarian Cancer Research; Board on Health Care Services; Institute of Medicine; National Academies of Sciences, Engineering, and Medicine. Ovarian Cancers: Evolving Paradigms in Research and Care. Washington (DC): National Academies Press (US); 2016 Apr 25. 1, Introduction and Background.
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