Modulation of Cholesterol Metabolism Improves Response to Enzalutamide Treatment in Prostate Cancer

Objectives Prostate cancer (PCa) growth is mediated by androgens via activation of androgen receptor (AR). Accordingly, androgen deprivation therapy (ADT) is the gold standard for the treatment of advanced PCa, but progression to castration-resistant PCa (CRPC) follows. Enzalutamide (ENZ) is an AR antagonist used for the management of CRPC. However, patients acquire resistance to the drug in a short period. As cholesterol metabolism is dysregulated in PCa and lipogenesis is upregulated by AR signaling, we hypothesized that inhibition of cholesteryl ester formation and suppression of lipogenesis by blockage of sterol-O-acyltransferase 1 (SOAT1) could enhance the response to ENZ.