Dr. Sandeep Kumar Mittan
Vol. 1, Jan-Jun 2016
Abstract:
Cervical Cancer (CC) is the third most common cancer in women worldwide. When invasive cancer is diagnosed thecure rate is low resulting in high mortality. The treatment response of invasive and metastatic CC remains unpredictable. There is an unmet need for targeted therapies in CC based on genetic/epigenetic pathways. Towards this goal, utilizing the published evidence of inactivation of tumor necrosis factor receptor superfamily genes (TNFRSF10C/DcR1, and TNFRSF10D/DcR2) play a role in apoptosis in CC, the present proposal seeks to further investigate this pathway to develop clinically significant therapeutic approach to stratify patients for TRAIL-combination therapy. We will investigate the molecular mechanisms regulated by TNFRSF10C and TNFRSF10Dinactivation in TRAIL-mediated apoptosis in CC.Using a panel of well characterized CC cell lines, we will address (i) the contribution of relative roles of TNFRSF10Cand TNFRSF10D gene inactivation in vitro in TRAIL-combination therapy in inducing apoptosis by depletionand over-expression approaches, and (ii) determine the functional role of inactivation of these genes intumoricidal activity of TRAIL-combination therapy in CC tumor xenograft model. Success of these research studies will provide an essential platform for the development of a new molecular based test for stratification of CC for TRAIL targeted therapy.