Evaluating Poor Outcome for Manitoba Women with Ovarian Cancer

Abstract

Epithelial ovarian cancer (EOC) is the most lethal form of gynecological cancer. EOC patients have a low survival rate primarily due to the late stage at which the disease is diagnosed (typically after metastasis), and the high rate of recurrent disease. While the majority of patients respond to initial chemotherapy [typically with a platinum agent (carboplatin) and a taxane (paclitaxel)], up to 75% of EOC patients will relapse within 18 months with chemotherapy-resistant disease. There is a desperate need to identify markers of resistance and novel pathways that may be targeted for treatment. Experiments have been conducted to gain insight into cell surface markers and/or signalling pathways associated with EOC drug resistance. Altered cell surface expression of several candidate pathways has been identified in a drug-resistant EOC cell line, A2780-cp. To extend these studies, further validation of cell surface protein expression will be conducted using additional EOC cell lines and EOC cells isolated from EOC patient ascites. Several serial samples of EOC cells isolated from patients before and after development of drug resistance are also available for testing and validation. Cell surface marker expression will be correlated with clinical parameters indicating platinum drug resistance. The student will learn to assess clinical data regarding patient response to chemotherapy. Moreover, experiments to alter cell surface marker expression in the drugresistant A2780-cp and drug-sensitive A2780-s cell lines will be done to assess the contribution of candidate markers/signaling pathways to development of drug resistance. The proposed studies will test the hypothesis that candidate cell surface markers can be used to predict formation of clinical chemotherapy resistance.