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The combined effect of hormones and inflammatory components on development of ovarian cancer - Dr. Lital Kalich-Philosoph

Epithelial ovarian cancer (EOC) is the most lethal of all gynecologic malignancies. In 2013, about 22,240 women in the United States have been diagnosed with invasive EOC and an estimated 14,000 of them would die. Nevertheless, the pathogenesis of this disease is poorly understood.  The occurrence of EOC is highly correlated with advanced age and shows increased aggressiveness after menopause. A major characteristic of menopause is high circulating levels of gonadotropic hormones. A role for these gonadotropins has been implicated in a variety of different aspects of ovarian cancer tumorigenesis, including cell proliferation, migration and invasion. Furthermore, a long-term follow-up study has shown an elevated risk of ovarian cancerous transformation in women who received gonadotropins treatment for infertility. There is indeed a significant correlative relationship between chronically elevated gonadotropin levels and ovarian cancer development, but the causal relationship between these hormones and ovarian cancer patients remains inconclusive. Cancer has long been considered a disease that mimics an “unhealed wound,” and inflammatory cell participation in tumor progression has been demonstrated. Along this line, the involvement of inflammatory signals in promoting ovarian cancer progression and their elevated expression during menopause has been reported. Moreover, in a recent study, we demonstrated that inflammation is included among the other responses of the ovary to gonadotropins. Taking this information into consideration we hypothesize that gonadotropins combined with an inflammatory microenvironment promote cancer development in the ovary. The overall goal of this study is to understand the conjunction of hormonal and inflammatory mechanisms involved in the complexity of ovarian cancer. The results of our research could significantly contribute to the development of therapeutic targets for prevention/treatment of postmenopausal cancer patients. Furthermore, the lack of awareness to the possible hazardous influence of high doses of gonadotropins administered to young women who undergo in vitro fertilization (IVF) raises an additional serious concern. Therefore, an even higher significance of this study is in evaluating the risk of hormonal treatment and recommending the use of alternative protocols that will allow fulfilling the dream of parenthood with a reduced hazard for cancer development.