Cellular androgen content influences enzalutamide agonism of F877L mutant androgen receptor.

ABSTRACT: Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) - the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR. This insight led to the development of the AR antagonist enzalutamide. However, resistance to enzalutamide invariably develops, and disease progression is nearly universal. One mechanism of resistance to enzalutamide is an F877L mutation in the AR ligand-binding domain that can convert enzalutamide to an agonist of AR activity. Howeve

SUBMITTER: Coleman DJ 

PROVIDER: S-EPMC5130036 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature