Androgen receptor: structure, role in prostate cancer and drug discovery

Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2-3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein.

Indexed on Europe PMC as PubMed record 24909511 (DOI 10.1038/aps.2014.18). Its title names Androgen receptor and its text names Prostate cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, review-article, Review, Research Support, N.I.H., Extramural). It was matched automatically to the idea "Destroy the truncated androgen receptor that hormone drugs cannot touch" and no figure has been checked by an editor.