Androgen receptor abnormalities in castration-recurrent prostate cancer

The androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Despite the success of androgen-deprivation therapy, remission occurs in almost all cases. This stage of the disease is called castration-recurrent PCa (CRPC). CRPC cells adapt to low circulating levels of androgens, and active AR is maintained by numerous cellular mechanisms. Some mutations in the AR make it more responsive to lower androgen levels or other steroids. Furthermore, in this advance stage of the disease, PCa cells express the enzymes necessary for de novo synthesis of androgens. AR is also activated in a ligand-independent manner. Therefore, it is important to understand the mechanisms of AR activation and its deregulation during CRPC. The purpose of this article is to discuss mechanisms that are involved in modulation of AR activity and specificity.