2014 Volume 73 Issue 3 Pages 134-139
The androgen receptor (AR) plays a critical role in the progression of prostate cancer. At present, the only established treatment for metastatic castration-resistant prostate cancer (CRPC) is monotherapy with docetaxel. However, several studies have shown that the majority of CRPC express AR and androgen-responsive genes, indicating that the AR signaling pathway is still functional under androgen-depleted conditions. The main mechanisms underlying the progression of prostate cancer into a castrate-resistant state are hypersensitivity to AR, promiscuous AR activity and outlaw AR pathways that bypass the need for androgens. Therefore, understanding these mechanisms has promoted the development of new anti-androgens and androgen-depleting agents. Recently, several therapies targeting the androgen signaling pathway have come to market. Notably, promising results have been obtained in clinical trials with enzaltamide, a small-molecule AR antagonist that prevents nuclear translocation and DNA binding without agonist activity, and with abiraterone acetate, a prodrug, low molecular weight inhibitor of a rate-limiting enzyme in androgen biosynthesis. Herein, we review the androgen signaling pathway and novel drugs targeting this pathway for the management of CRPC.
