Androgen Receptor Dependence

Androgens and the androgen receptor (AR) play crucial roles in the biology of normal and diseased prostate tissue, including prostate cancer (PCa). This dependence is evidenced by the use of androgen depletion therapy (ADT) as the primary treatment for locally advanced, metastatic, or relapsed PCa. This dependence is further evidenced by the various mechanisms employed by PCa cells to re-activate the AR to circumvent the growth-inhibitory effects of ADT. Re-activation of the AR during ADT is central to the disease evolving into the lethal castration resistant PCa (CRPC) phenotype, which is responsible for nearly all PCa mortality. Thus, understanding the regulation of AR and AR signaling is important for understanding the development and progression of PCa. This understanding provides the foundation for development of newer approaches for targeting CRPC therapeutically.