Improving Strategies in the Development of Protein‐Downregulation‐Based Antiandrogens

Abstract

AR plays a crucial role in the occurrence and development of prostate cancer (PCa) and its signaling pathway remains active in castration-resistant prostate cancer (CRPC) patients. The drug resistance of current clinical used antiandrogens is a major challenge for the treatment of PCa, thus the development of new generations of antiandrogens is highly demanded. Recently, strategies of the downregulation of AR protein have been attracted the huge attention due to its potential in the discovery and development of new antiandrogens, including the stabilizers of G-Quadruplex, inhibitors of ROR-γ, AR targeting PROTACs, and other selective AR degraders (SRADs), which are able to conquer current resistances such as the acquired mutation of AR, the expression of AR variable splices, or over-expression of AR. This review summarized the various strategies for down-regulating AR protein, at either mRNA or protein level, thus providing new ideas for the development of the promising antiandrogens.