Standard androgen deprivation therapy for prostate cancer

Prostate cancer is the second leading cause of cancer death for men in the United States. Tumor progression is driven by conversion of testosterone by 5a-reductase to dihydrotestosterone, which both bind and activate the androgen receptor (AR). Androgen deprivation therapy (ADT), or depletion of gonadal testosterone, blocks this sequence of events, and has been the mainstay of upfront systemic treatment for prostate cancer for 70 years. ADT is achieved by surgical or pharmacological means. Although the majority of circulating testosterone is depleted, intratumoral testosterone and dihydrotestosterone persist after ADT, implying the existence of alternative source(s) of these androgens. Importantly, the generation of intratumoral androgens and ensuing AR activation is a major mechanism that drives resistance to ADT. The goal of this review is to summarize the approaches to ADT, effects on the tumor, clinical benefits and mechanisms of resistance.