AR, Overview

The androgen receptor (AR) is a nuclear hormone receptor that plays a key role in the development of the prostate and progression of prostate cancer (PCa). AR is the initial target for treatment in hormone dependent PCa, where inhibition of AR activity results in a decrease in tumor volume and increased survival. However, PCa often returns as castration-resistant prostate cancer (CRPC) due to several factors including AR overexpression, reactivation of the full-length receptor (ARFL), and expression of constitutively activate truncated AR-variants (AR-Vs) that lack the ligand binding domain. Upon reactivation of AR-FL and expression of AR-Vs, traditional methods of treatment targeting the ligand binding domain are ineffective. Targeting the evolutionarily conserved N-terminal domain, DNA binding domain (DBD) or using transcription factors that interact with AR will be key in developing new treatments for PCa.