Characterizing Mechanisms of Resistance to Androgen Deprivation in Prostate Cancer
Annual rept. 15 Aug 2013-14 Aug 2014
DANA-FARBER CANCER INST BOSTON MA
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Despite significant advances in the treatment, prostate cancer PCa, remains a leading cause of cancer death among men. Androgen deprivation therapy ADT constitutes the main therapeutic option for patients with advanced PCa. However, the major cause of death in men with metastatic prostate cancer involves progression to castration-resistant prostate cancer CRPC. Characterizing mechanisms of resistance to ADT could enable the development of more effective therapeutic strategies. We performed a systematic genome-wide suppressor RNAi screen in the androgen-sensitive LNCaP cells, and identified genes whose silencing drives resistance to ADT in androgen-sensitive LNCaP cells, using nextgen sequencing. Performing cell viability assays, we validated the ability of shRNAs against 20 top-tier genes to increase proliferation under androgen-deprived conditions,and also tested their effect on cell proliferation in the presence of the direct AR antagonist MDV3100. This study has identified several genes whose silencing may modulate resistance to ADT in prostate cancer.
- Medicine and Medical Research