Ovarian cancer is the leading cause of death among gynecological (GYN) cancers. More than half of the women diagnosed with ovarian cancer die from it within 5 years. If detected early, the prognosis improves dramatically: 95% of patients are still alive 5 years after diagnosis. However, there are no detection means for the early diagnosis of ovarian cancer, and only few treatment options are available today.

The need to develop a reliable screening test for ovarian cancer cannot be overemphasized. We also must design more specific and efficient therapeutic strategies if we are to combat this aggressive disease. Most importantly, we must learn not only how to diagnose and treat ovarian cancer, but also how to prevent it. This may be the only way to eliminate ovarian cancer as a malignant disease. None of these goals can be achieved unless we first gain a better understanding into the pathogenesis of ovarian cancer. The major risk factors that are associated with this disease need to be identified, and how they contribute to the development of ovarian cancer also must be determined.

Endometriosis, a benign disease of the GYN tract that affects up to 20% of women of reproductive age, has long been recognized as one of the major risk factors that predispose women to ovarian cancer. The mechanism by which it does so remains unknown. Epidemiologic studies have consistently shown an association between ovarian cancer and endometriosis. As mentioned earlier, endometriosis is a prevalent disease; however, only 0.3%-1.6% of patients with endometriosis go on to develop ovarian cancer. It is thus critical to determine what the genetic changes are that favor the potential malignant transformation of endometriosis to ovarian cancer.

Gaining a better understanding into the pathogenesis of endometriosis and how it overlaps with that of ovarian cancer has been difficult in the absence of an animal model of the two diseases. We aim to make a unique contribution to the ovarian cancer research field by developing an animal model of ovarian cancer associated with endometriosis.

The generation of such a model has the potential to benefit ovarian cancer research in many ways. First, it will allow us to evaluate the relative roles of oncogenes and tumor suppressor genes in ovarian tumorigenesis and their ability to cooperate in tumor formation. Second, using this model we will able to determine whether endometriosis gives rise to ovarian cancer or if the two conditions, although associated with each other, are in effect independent events. We will thus begin to uncover the genetic and pathophysiological links between endometriosis and ovarian cancer. Third, it will facilitate the identification of key signaling events that are responsible for tumor development and progression. This will lead to the discovery of new therapeutic targets and biomarkers for the early detection of ovarian cancer. Last but not least, such a system will be instrumental in testing the efficacy of various chemotherapeutic and chemopreventive agents as they become available. The development of an animal model will provide a means to conduct preliminary therapeutic and diagnostic screenings in a relevant in vivo setting, which should lead to the design of more rational clinical trials. The studies we are proposing, if validated in humans, will have important implications for the diagnosis, treatment, and chemoprevention of ovarian cancer.