Androgen Receptor Cofactors in Prostate Cancer: Potential Therapeutic Targets of Castration-Resistant Prostate Cancer

Masaki      Shiota; Akira      Yokomizo; Naohiro      Fujimoto; Seiji      Naito

Abstract

Androgens, acting through the androgen receptor (AR), are responsible for many male reproductive and nonreproductive functions. Moreover, aberrant androgen/AR signaling plays a critical role in androgen-dependent prostate cancer (PCa) as well as castration-resistant prostate cancer (CRPC). The formation of a productive AR transcriptional complex requires AR cofactors that interact functionally and structurally with the AR. Since the discovery of the first such cofactor in 1995, an ever increasing number of proteins have been identified as AR coactivators or corepressors. The expression and function of several AR cofactors have been investigated in PCa, and a clear link between AR cofactors and the development and progression of PCa has been identified. Recently, AR splice variants in CRPC were reported, which display significant constitutive activity in the absence of ligand. Then, this discovery revolutionized the concept of AR cofactors in CRPC. The current review aims to provide an overview of AR cofactor proteins in the context of PCa. In addition, we discuss the potential of AR cofactors as novel therapeutic targets for PCa, particularly for CRPC.

Keywords: Androgen, androgen receptor, cofactor, heat shock protein 90, prostate cancer, target therapy, splice variant, DEAD box polypeptide 5, dihydrotestosterone, heterochromatin protein, prostatic intraepithelial neoplasia, protein arginine methyltransferase 1