Abstract IA24: Developing and deploying experimental models systems towards novel drug discovery in ovarian cancer.

Ovarian cancer carries significant mortality in the absence of effective methods for prevention and screening. Preventive salpingo-oophorectomy is currently the only method known to reduce the risk of ovarian cancer-related death. Histopathological analyses of these surgical specimens indicate that a high proportion of ovarian cancers in women at high risk and in the general population arise from the fallopian tube. This paradigm shift in our understanding of the cell of origin for the most common subtype of ovarian cancer, high-grade serous carcinoma, has sparked a major effort within the research community to develop new and robust model systems to study the fallopian tube epithelium, it susceptibility to neoplastic transformation, and opportunities for therapeutic intervention. These models include primary cell line cultures, fallopian tube-derived lines, epithelial-stromal co-cultures, genetically-engineered mouse models, and patient-derived tumor xenografts or ‘avatars’. There has also been a re-evaluation of the fidelity of established ovarian cancer cell lines and the need to develop new lines that represent the human disease. Critical to this effort is the need to go beyond genomics and critically evaluate the functional utility of new cell lines. The deploying of these new models is already have a profound effect on our ability to identify unique susceptibilities in ovarian cancer through genetic screens, chemical screens, and targeted approaches. In addition, the search for novel biomarkers that can play a role in early detection or prognostication is being re-defined by looking at the fallopian tube fimbria as the source. Citation Format: Ronny Drapkin, Anna Budina, Yi Feng, Kai Doberstein. Developing and deploying experimental models systems towards novel drug discovery in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA24.