Ovarian cancer ranks first among gynecological cancers in the number of new deaths each year. An estimated 25,200 women will be diagnosed with and 14,500 will die from ovarian cancer in 1999.¹ Ovarian cancer is often without overt symptoms until late in its development, and has a 5-year survival rate of only 46%.

The Department of Defense (DOD) Ovarian Cancer Research Program (OCRP) was established in fiscal year 1997 (FY97) by Joint Appropriations Bill 104-864, which provided $7.5M for research in ovarian cancer. The overall goal of the OCRP is to promote innovative, integrated, multidisciplinary research efforts that will lead to a better understanding and control of ovarian cancer. The OCRP is designed specifically to: (1) advance ovarian cancer prevention strategies through enhanced understanding of ovarian cancer etiology; (2) engage experts from multiple disciplines in collaborative ovarian cancer research efforts; and (3) foster the development of a sustained national ovarian research enterprise. In FY98, Joint Appropriations Bill 105-265 provided $10M to continue the OCRP. An additional $10M was provided to continue the OCRP in FY99.

In FY97-99, Congress appropriated $27.5M for peer-reviewed ovarian cancer research. Table B-3 in Appendix B summarizes the directions from Congress for the OCRP appropriations, the program’s withholds and management costs, and the investment strategy executed by the program. Prior to receipt of funds by the office of the Congressionally Directed Medical Research Programs (CDMRP), Congress and the DOD withhold funds for designated initiatives. In addition, the CDMRP sets aside funds for program development, scientific peer review, programmatic review, and the administration of grants/contracts through the entire period of performance up to 7 years (see Appendix B). The investment strategy executed is consistent with Congressional language and reflects the program’s vision.

The vision of the OCRP is to prevent ovarian cancer. The program’s mission is to promote research directed toward a comprehensive ovarian cancer prevention program. Scientific ventures that represent underinvestigated avenues of research or novel applications of existing technologies are highly sought. In addition, research that addresses the needs of minority, low-income, rural, and other underrepresented and/or medically underserved populations is encouraged.

——FY97 Program

Program Project Awards to National Cancer Institute (NCI)-designated Comprehensive Cancer Centers were used to develop novel ovarian cancer prevention strategies. The effort focused on epithelial ovarian cancer. Proposals required the incorporation of at least two projects, integrated around a common theme relevant to prevention. Eligible institutions were restricted to Comprehensive Cancer Centers, as defined by the National Institutes of Health NCI. Three Program Project Awards were funded with FY97 funds.

——FY98 Program

The programmatic strategy for FY98 was implemented by a solicitation for Program Project Awards. These awards were designed to incorporate at least two individual research projects integrated around a common theme: addressing ovarian cancer prevention and/or etiology. In an attempt to foster new directions and bring new investigators into the field of ovarian cancer research, one research project needed to be an Idea project, and the same or a different research project needed to have a New Investigator designated as the Project Director. Five Program Project Awards were funded with FY98 funds.

The following tables reflect the funding summaries, in terms of dollars and number of awards, for the FY97-98 OCRP.

——FY99 Program

The programmatic strategy for the FY99 OCRP was implemented by a solicitation in the 21 July 1999 Program Announcement for proposals in subcategories of Idea Awards and New Investigator Awards. The intent of the Idea Award category is to encourage innovative approaches to ovarian cancer research. The intent of New Investigator Awards is to prepare new, independent investigators (Assistant Professor or equivalent with no more than 6 years of experience in the field of ovarian cancer) for careers in ovarian cancer and to attract more senior investigators new to the ovarian cancer field. The FY99 program emphasis areas are etiology, prevention, diagnosis, and quality of life.

——FY00 Program Plans

The Joint Conference Committee Report 106-371 specifies $12M for peer-reviewed ovarian cancer research. Vision setting for the FY00 program will occur in February 2000. At that time an investment strategy will be developed, taking into account Congressional language, recommendations from scientific and advocacy groups, and gaps in research funding.

Program Project Awards were developed by the OCRP Integration Panel and Program Staff in FY97-98 to encourage the development of integrated multidisciplinary research. Efforts were made to develop novel ovarian cancer prevention strategies with the goal of building a national infrastructure.

A total of eight awards have been made in the FY97-98 OCRP. These awards support large, multidisciplinary Cancer Centers. Research funded by this relatively new program is already showing signs of productivity and promise.

——Infrastructure

The FY97 and FY98 OCRP funded eight Program Project Awards for the establishment of regional centers for the study and treatment of ovarian cancer. It is anticipated that these infrastructure awards will invigorate the research community, bring new investigators into the field of ovarian cancer, and make strides toward the prevention of ovarian cancer. Three of the most recent NCI Specialized Program of Research Excellence (SPORE) awardees are OCRP DOD grant recipients. Investigators have acknowledged that the DOD awards contributed to their ability to obtain SPORE funding.

——Training

The OCRP is also making a significant investment to stimulate talented new investigators, as well as superb established investigators currently working in other fields, to join the arena of ovarian cancer research. The FY99 OCRP is soliciting new investigator proposals to provide opportunities for new investigators and more senior investigators to enter the field of ovarian cancer research.

——Scientific Achievements

While the OCRP is relatively young, it is anticipated that funded research will provide the framework for contemporary and future scientific discoveries. To date, eight proposals have been awarded with FY97-98 funds. The following are short descriptions of areas in which the studies hope to make accomplishments.

Etiology and Chemoprevention. Researchers at Duke University Medical Center will attempt to elucidate the etiology of ovarian cancer and translate this knowledge into effective preventive strategies. The principal investigator (PI) will attempt to confirm an association between high numbers of lifetime ovulatory cycles and alterations of the p53 tumor suppressor gene in ovarian cancers. Also, the PI will explore the mechanism and potential use of progestins as ovarian cancer chemopreventive agents.

Investigators at the University of Texas will study chemoprevention of ovarian cancer. The PI has three projects planned: (1) to conduct a study in female rhesus monkeys to explore the underlying biologic mechanisms of oral contraceptives; (2) to conduct a study of the efficacy of oral contraceptives and synthetic vitamin A to induce similar changes in women at risk for ovarian cancer; and (3) to explore mechanisms underlying the chemopreventive activity of oral contraceptives and synthetic vitamin A.

Familial Risk. A study from the Fox Chase Cancer Center will conduct research in ovarian cancer prevention and control focusing on familial risk of cancer, the behavioral factors influencing the decision to undergo prophylatic oophorectormy, and the effect of chemoprevention agents on precancer structural and molecular markers of carcinogenesis.

Molecular Markers, Candidate Genes, and Genetic Alterations. Several studies funded by the OCRP will examine molecular markers, genes, and genetic alterations that may play a role in ovarian cancer. For instance, investigators from the Fred Hutchinson Cancer Research Center will study the use of novel technologies to identify and investigate molecular markers for ovarian cancer screening. The study will involve the collection and analysis of tissue and serum of women undergoing ovarian-related surgery.

A study from the Jonsson Comprehensive Cancer Center will explore the genetic definitions and phenotypic determinants of human ovarian carcinomas. Specifically, the PI plans to identify genes that are responsible for causing ovarian epithelial cells to become malignant; study the interactions between the BRCA1 and p53 genes; and develop an animal model of ovarian cancer that can be used to validate the importance of candidate genes in ovarian tumor formation.

Research conducted at the Mayo Foundation will study the characterization of genetic alterations in ovarian cancer. The PI plans to identify genes that are aberrantly regulated or mutated during ovarian cancer development and use these genes for future studies aimed at developing important prognostic markers, immunology strategies to target cancer, and intelligent prevention strategies.

A study from Brigham and Women’s Hospital will attempt to develop multidisciplinary strategies in the prevention and early detection of ovarian cancer. The PI has four projects planned: (1) to study genetic changes in ovarian cancer cells confined to the ovary; (2) to characterize a novel enzyme (Protease M) and evaluate its potential as an early diagnostic marker for ovarian cancer; (3) to study the effect of hormones on growth of normal ovarian cells; and (4) to use lipids to develop a highly sensitive and specific marker for early detection of ovarian cancer.

Angiogenesis. A study from the University of Minnesota will explore the role of angiogenesis in the etiology and prevention of ovarian cancer. One of the major goals of the program project is to identify how ovarian cancer cells induce new blood vessel development and disseminate in the abdominal cavity. The other major aim of the study is to develop methods to inhibit blood supply to the tumors and thereby prevent their growth.

Chair, Judith S. Kaur, M.D.: Consultant in medical oncology, Mayo Clinic, and Assistant Professor of Oncology, Division of Medical Oncology, Mayo Medical School. Served on Task Force on Cancer in the Socioeconomically Disadvantaged for the National Board of American Cancer Society (ACS), as Chairperson of the Native American Subcommittee for the State of North Dakota Cancer Control Project, and as Member of the Cancer Prevention Committee of the Gynecologic Oncology Group. Discipline(s): Medical Oncology.

Michael J. Birrer, M.D., Ph.D.: Chief, Molecular Mechanisms Section, Department of Cell and Cancer Biology, Division of Clinical Sciences, NCI, National Institutes of Health (NIH); Assistant Professor, Uniformed Services University of the Health Sciences; Attending Physician, National Naval Medical Center and NCI Clinical Center. Discipline(s): Molecular Biology.

Holly H. Gallion, M.D.: Professor, Department of Obstetrics and Gynecology, University of Kentucky; Full-time Staff, University of Kentucky Medical Center. Serves on a variety of associations including the Ovarian Committee of the Gynecologic Oncology Group, the Executive Committee and Vice President of the Society of Gynecologic Oncology. Discipline(s): Genetics/Gynecologic Oncology.

David Gershenson, M.D.: Director, Blanton-Davis Ovarian Cancer Research Program; Anderson Clinical Faculty Chair for Cancer Treatment and Research, and Professor and Chair, Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center. Editor of Gynecologic Oncology and Operative Techniques in Gynecologic Surgery. Member of the Division of Gynecologic Oncol-ogy of the American Board of Obstetrics and Gynecology and the Gynecologic Oncology Group Ovarian Cancer Committee. Discipline(s): Gynecologic Oncology.

Thomas Hamilton, Ph.D.: Senior Member, Department of Medical Oncology, and Leader, Ovarian Cancer Program, Fox Chase Cancer Center; Adjunct Professor, Department of Chemistry, Lehigh University; and Co-Chairman of the Gynecologic Oncology Group Committee on Experimental Medicine. Discipline(s): Drug Resistance, Drug Development.

Enrique Hernandez, M.D.: Professor of Obstetrics and Gynecology and of Pathology, Director, Division of Gynecologic Oncology, Temple University School of Medicine, Past President of the Mid-Atlantic Gynecologic Oncology Society. Discipline(s): Gynecologic Oncology.

William J. Hoskins, M.D.: Deputy Physician Chief for Disease Management and Chief of Gynecology Services, Department of Surgery, Memorial Sloan-Kettering Cancer Center; Avon Chair in Gynecologic Oncology Research; Professor, Department of Obstetrics and Gynecology, Cornell University Medical College. Current Vice-Chairman of the Gynecologic Oncology Group, and member of the PDQ External Advisory Board of the NCI. Discipline(s): Gynecologic Oncology.

Hedvig Hricak, M.D., Ph.D.: Professor of Diagnostic Radiology, Radiation Oncology, Urology, and Gynecology, and Chief of Abdominal Imaging Section, University of California, San Francisco. Ph.D. in Oncology. Discipline(s): Radiology/Genital Urinary.

Beth Karlan, M.D.: Director, Gilda Radner Ovarian Cancer Program, and Director, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center; Associate Professor, Department of Obstetrics and Gynecology, University of California, Los Angeles. Discipline(s): Molecular Biology.

Ann Kolker: Executive Director, Ovarian Cancer National Alliance, national umbrella organization dedicated to increasing public and professional understanding of ovarian cancer and advocating for increased research for more effective diagnostics and treatment. Serves on Institutional Review Board of NCI. Ovarian cancer survivor. Discipline(s): Consumer.

Robert J. Kurman, M.D.: Richard W. TeLinde Distinguished Professor of Gynecologic Pathology, Departments of Gynecology-Obstetrics and Pathology, The Johns Hopkins School of Medicine; Director of Gynecologic Pathology, The Johns Hopkins Hospital. Consultant for the American Registry of Pathology. Discipline(s): Pathology.

Maurie Markman, M.D.: Director, Cleveland Clinic Taussig Cancer Center; Chairman, Department of Hematology/Medical Oncology; and The Lee and Jerome Burkons Research Chair in Oncology, The Cleveland Clinic Foundation. Discipline(s): Chemotherapy, Experimental Therapeutics.

Cindy H. Melancon, R.N., M.N.: Editor, monthly newsletter CONVERSATIONS: The Newsletter for Those Fighting Ovarian Cancer; Founding Member of National Ovarian Cancer Coalition, Boca Raton, Florida; Founding Board Member and Vice-President of Ovarian Cancer National Alliance, Washington, DC. Ovarian cancer survivor. Discipline(s): Consumer.

Geraldine Padilla, Ph.D.: Professor and Associate Dean of Research, University of California, Los Angeles School of Nursing. Ph.D. in Psychology/Public Health. Member of the Quality of Life Task Force and the Cancer Control Committee and Patient Advocacy Committee, ACS, and the Arthritis Foundation Southern California Education Committee. Discipline(s): Quality of Life.

Eddie Reed, M.D.: Head, Medical Ovarian Cancer Section, Medical Branch, Division of Clinical Sciences, NCI. Past member of several NIH committees of the Gynecologic Oncology Cooperative Study Group. Currently on the Howard Hughes Medical Institute Board of Advisors. Has received several awards including two U.S. Public Health Service Commendation Medals for his work on ovarian cancer. Discipline(s): Experimental Therapy.

Harvey A. Risch, M.D., Ph.D.: Associate Professor of Epidemiology and Public Health, Yale University School of Medicine. Ph.D. in Biomathematics. Member of several national organizations including the Society for Epidemiologic Research and the Biometry Society, and Fellow of the American College of Epidemiology. Discipline(s): Epidemiology.

Elwood L. Robinson, Ph.D.: Professor and Chair, Department of Psychology, North Carolina Central University. Ph.D. in Clinical Psychology. Research interests include physical and mental stress on the cardiovascular system, particularly in African Americans. Discipline(s): Clinical Psychology.

Mary Jackson Scroggins: Member of the Board of Directors of the Ovarian National Alliance. Founder and publisher of Sister Circle, a quarterly newsletter focused on ovarian cancer and other women’s health issues specifically targeted at women of color and other underserved women. Previously served on peer review panels of the OCRP. Ovarian cancer survivor. Discipline(s): Consumer.

Michael A. Steller, M.D.: Head, Gynecologic Oncology, Surgical Branch, National Cancer Institute. Holds appointments in Departments of Gynecology and Obstetrics, The Johns Hopkins University Medical Institutes and Georgetown University School of Medicine. Member of steering committee, ASCUS/LSIL Clinical Management Trial at the NCI, and several gynecological and oncological societies. Discipline(s): Experimental Therapy.

Robert C. Young, M.D.: President, Fox Chase Cancer Center. Serves on several editorial boards including the Journal of Clinical Oncology and Oncology Times. Currently is on the National Cancer Policy Board and the Board of Scientific Advisors to the NCI. Served in a variety of positions for several national organizations including a position on the Board of Directors for the American Association of Cancer Institutes, the American Cancer Society and the American Society of Clinical Oncology. Discipline(s): Medical Oncology.