About EIF’s Women’s Cancer Programs
The Entertainment Industry Foundation (EIF), as a leading charitable organization of the entertainment industry, has distributed hundreds of millions of dollars to support charitable initiatives addressing critical health, education and social issues.

Through its Women’s Cancer Programs, EIF has a remarkable track record in raising awareness and funds in the fight against cancer. EIF’s funding strategy is results-driven, bringing together some of the very best scientists and institutions in the country to collaborate in groundbreaking research projects to fast track better prevention methods and improved therapies for treatment of breast cancer.

EIF’s targeted grants have helped accelerate research that has contributed to the development of the breakthrough breast cancer treatment Herceptin®, the first successful drug that seeks out a particular gene found in one of three cases of the most aggressive form of breast cancer. EIF grants have also supported other state-of-the-art therapies bringing new and innovative treatment approaches to breast cancer worldwide.

With Callaway Golf Foundation Support
Through a $1 million donation from the Callaway Golf Foundation to EIF’s Women’s Cancer Programs, the Callaway Golf Foundation Women’s Cancer Initiative (CGFWCI) has been established at four outstanding cancer institutions to fast-track breakthrough treatments and test to improve ovarian cancer and outcomes.  The group’s ultimate goal is to significantly reduce the number of women who die each year from ovarian cancer.

Led by Dr. Beth Karlan, the initiative represents a collaborative, multi-site undertaking designed to advance treatment of ovarian cancer through molecular profiling, biomarker discovery and targeted therapy development.   The consortium includes:

Beth Y. Karlan, M.D.
Board of Governors' Endowed Chair in Gynecologic Oncology and Director
Cedars-Sinai WCRI at the Samuel Oschin Comprehensive Cancer Institute (Lead Institution)
Expertise: Ovarian Cancer Early Detection and Biomarker Discovery

Early detection is a primary objective of ovarian cancer research because of its promise for improved survival and quality of life.  The overall five year survival for women diagnosed with ovarian cancer is 50%, but when the cancer is detected early, while it is still confined to the ovaries, prolonged survival and even cure is possible for over 95% of these women.  Unfortunately, at the current time the majority of cases are diagnosed at a late stage after the tumor has spread widely, in large part, due to a lack of effective screening and early detection techniques.  Ovarian cancer mortality could be reduced dramatically, even without advances in therapy, if a majority of the women affected with ovarian cancer could be diagnosed at an early stage.  We have had a long standing interest in discovering effective means of early detection since our initiation of the Gilda Radner Ovarian Cancer Detection Program in 1991.  In addition to our ongoing studies of women at high risk for ovarian cancer due to their inherited genetic predisposition to the disease, we are working to discover serum biomarkers that can be used as a screening test for all women.

The focus of these efforts will be on the identification of genomic and proteomic profiles that comprise ovarian cancer-specific signatures. Profiles will be validated using our robust human tissue resources and matching serial serum samples in order to optimize and refine the ability of the biomarkers to predict disease status.  It is generally agreed that a panel of tumor markers will be required to achieve adequate sensitivity and specificity for early stage disease.  After more than 15 years of banking gynecologic tissue specimens, the Ovarian Tissue and Clinical Database Core Facility is a cornerstone of the WCRI research program.  It provides a rich resource of clinical specimens from patients with ovarian carcinoma, from women at high risk of ovarian cancer due to an inherited predisposition, and from women with normal ovaries that have been removed for benign indications.  Additionally, the core establishes, characterizes and maintains in vitro and in vivo models (primary monolayer cell cultures and murine xenografts, respectively) to facilitate research aimed at understanding genetic mechanisms involved in ovarian carcinogenesis and to support our preclinical investigations of molecular-targeted therapies.  An additional strength of our core facility is its state-of-the-art relational database system that links all patient demographic, epidemiologic, and medical information with each banked specimen.  This “linkage” facilitates translational research by allowing us to correlate laboratory research discoveries, clinical observations, and patient characteristics. 

WCRI has begun to molecularly profile ovarian cancer’s to identify novel molecular biomarkers for early detection and monitoring.  Our preliminary data demonstrate that gene expression profiling can differentiate between the various ovarian cancer histologic subtypes.  In addition, gene silencing by epigenetic mechanisms, such as DNA methylation, is now recognized as another critical trigger for neoplastic development and progression.  Our preliminary data demonstrate that DNA methylation patterns in ovarian cancers characterize some highly aggressive tumors that do not respond to conventional therapies. Soluble tumor DNA shed into the surrounding fluid and/or serum when cancer cells die represents a stable analyze that can be amplified and then utilized for biomarker determination.  Our goal will be to define the genetic and epigenetic fingerprints of ovarian cancer and to determine the molecular signatures most useful for diagnosis, early detection, and therapy design. 

David M. Gershenson, M.D. 
Chairman Gynecologic Oncology Department
University of Texas M. D. Anderson Cancer Center
Expertise: Tumor Angiogenesis and Molecular Targeting Strategies in Ovarian Cancer

Despite advances in surgery and chemotherapy, ovarian cancer remains the most common cause of mortality from a gynecologic malignancy. The majority of ovarian cancer patients respond to initial surgery and platinum-based chemotherapy, but of these about 70% will recur and succumb to disease. The poor outcome of ovarian cancer patients is due to widespread metastases and development of resistance to chemotherapy. Due to the poor survival of women with ovarian cancer, understanding the mechanisms contributing to ovarian cancer development and progression as well as novel therapeutic approaches are urgently needed.

Targeting the tumor vasculature (blood supply) is a particularly attractive therapeutic strategy because endothelial cells are thought to be inherently more genetically stable than tumor cells. One such strategy has included the use of a soluble VEGF decoy receptor, the VEGF Trap, comprised of fragments of VEGF receptor (VEGFR)-1 (flt1) and VEGFR2 (flk1, KDR). Our preclinical studies indicate that VEGF-Trap in combination with taxane chemotherapy is highly efficacious. Based on these findings we are initiating a clinical trial for treatment of patients with recurrent ovarian cancer using VEGF-Trap and docetaxel.

While VEGF-targeted strategies have shown promise in ovarian and other cancers, it is likely that additional targets will be required to further improve the therapeutic efficacy of anti-angiogenic approaches. To identify novel molecular targets in the ovarian cancer vasculature, we have performed recent studies to identify differentially overexpressed genes in the tumor endothelial cells as compared to normal ovarian endothelial cells. Using microarray profiling, we have identified a list of genes that are selectively overexpressed in the ovarian cancer vasculature. We are testing the functional significance of these targets using both in vitro and in vivo experimental models. Moreover, we have recently developed a highly efficient method of delivering short interfering RNA (siRNA) in vivo using neutral nanoparticles for therapeutic applications. This strategy gives us opportunities to block abnormally expressed genes that are not “druggable” with other approaches. In proof-of-concept studies, we have demonstrated that targeting the EphA2 tyrosine kinase with siRNA incorporated in nanoparticles was highly efficacious in pre-clinical models. Based on discussions with the FDA, we are performing formal toxicology studies prior to bringing this approach to clinical trials. We are developing siRNA-based anti-angiogenic approaches for targeting the differentially expressed genes in the tumor vasculature. We are also developing additional nanoparticles to deliver siRNA selectively to cell types of interest (for example, tumor associated endothelial cells or tumor cells).

In summary, we have developed highly innovative strategies that hold promise for providing new targeted therapies for ovarian cancer patients. Our work is supported by extensive preliminary data and is being carried out by a highly qualified, multi-disciplinary research team.

Richard R. Barakat, M.D. 
Chief, Gynecology Service Division of Gynecologic Oncology 
Memorial Sloan-Kettering Cancer Center
Expertise: Molecular Profiling of Ovarian Cancers to Predict Prognosis

The Gynecology Research Laboratory at Memorial Sloan-Kettering Cancer Center is one of the world’s leading research facilities in the study of ovarian cancer.  One of the main long-term aims of the Gynecology Research Laboratory at MSKCC is to develop new models to predict outcome in advanced ovarian cancer.  Though treatments are improving for patients with advanced ovarian cancer, those who succumb to disease ultimately develop platinum-resistant tumors.  We are developing a new class of predictive models using microRNAs, which are recently discovered short RNAs that regulate the expression of many genes in our body.  They are thought to be master regulators that control more function than classical messenger RNA.  Approximately 20% of women with newly diagnosed advanced ovarian cancer will have tumors that are resistant to platinum chemotherapy, the mainstay of treatment for this malignancy.  Currently we are unable to predict which patients are destined to have platinum resistant tumors.  The broad goal of our work is to identify a microRNA gene expression profile that predicts which patients are more likely to recur as well as further expand our knowledge of the molecular basis of ovarian cancer.  This will help us to tailor post-surgical treatments more effectively, such that we can offer additional therapy to those patients who are most likely to benefit.  This project should help to bring us one step closer to the promise of personalized cancer care.  Ovarian cancer is expected to strike 22,430 women in 2007 and lead to death in over 50% of those diagnosed. 

Robert E. Bristow, M.D.
Director, The Kelly Gynecologic and Oncology Service
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Expertise:  Ovarian Cancer Surgical Outcomes Analysis

Ovarian cancer is the leading cause of gynecologic cancer-related morbidity and mortality in the United States and many other developed countries worldwide. Improvements in clinical outcomes during the past 30 years have been incremental and have been the result of many different avenues of research including advances in surgical techniques, chemotherapeutic agents and delivery modalities, and supportive care. During this time period, standards of care for women with ovarian cancer have been firmly established. However, our research, as well as that of other investigators, indicates that a majority of women in the United States do not receive state-of-the-art care. The reasons for this are poorly understood. Consequently, outcomes analysis to elevate the standard of care for women with or at risk for ovarian cancer is an emerging and critically important field of investigation. A vital component of outcomes analysis for ovarian cancer is the identification of barriers to universal access to quality care. We have previously shown that these include patient demographic characteristics, qualifications (of lack thereof) of hospitals and individual providers, economic considerations, and the influence of third party payers to name just a few. Our current ovarian cancer research program is also focused on developing risk-adjusted measures of patient outcomes and healthcare provider performance and quantifying the short- and long-term impact of treatment on quality-adjusted patient survival. In addition to spotlighting the barriers to quality care, an equally important challenge is the development of model healthcare delivery platforms for women with ovarian cancer that are able to provide broadly accessible cutting-edge treatment at an economically affordable cost. Consequently, our multidisciplinary research team, comprised of experts in epidemiology, public health, health policy and management, and basic science research, is also focused on the cost-effectiveness and pharmaco-economic aspects of ovarian cancer outcomes analysis as well as the development of novel therapeutic agents.