Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Dec;140(3):223-38.
doi: 10.1016/j.pharmthera.2013.07.003. Epub 2013 Jul 13.

Androgen receptors in hormone-dependent and castration-resistant prostate cancer

Ayesha A Shafi  1 , Aihua E Yen, Nancy L Weigel
Affiliations
Review

Androgen receptors in hormone-dependent and castration-resistant prostate cancer

Ayesha A Shafi et al. Pharmacol Ther. 2013 Dec.

Abstract

In the United States, prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in males and the second leading cause of cancer-related death for men. The prostate is an androgen-dependent organ and PCa is an androgen-dependent disease. Androgen action is mediated by the androgen receptor (AR), a hormone activated transcription factor. The primary treatment for metastatic PCa is androgen deprivation therapy (ADT). For the most part, tumors respond to ADT, but most become resistant to therapy within two years. There is persuasive evidence that castration resistant (also termed castration recurrent) PCa (CRPC) remains AR dependent. Recent studies have shown that there are numerous factors that contribute to AR reactivation despite castrate serum levels of androgens. These include changes in AR expression and structure through gene amplification, mutation, and alternative splicing. Changes in steroid metabolism, cell signaling, and coregulator proteins are also important contributors to AR reactivation in CRPC. Most AR targeted therapies have been directed at the hormone binding domain. The finding that constitutively active AR splice variants that lack the hormone binding domain are frequently expressed in CRPC highlights the need to develop therapies that target other portions of AR. In this review, the role of AR in normal prostate, in PCa, and particularly the mechanisms for its reactivation subsequent to ADT are summarized. In addition, recent clinical trials and novel approaches to target AR are discussed.

Keywords: 5α-DHT; 5α-Dihdyrotestosterone; AA; ADT; AR; ARE; Abiraterone; Abiraterone Acetate; Androgen Deprivation Therapy; Androgen Receptor; Androgen Response Element; Androgen receptor; CAB; CRPC; Castration-Resistant Prostate Cancer; Castration-resistant prostate cancer; Combined Androgen Blockade; DBD; DHEA; DNA-Binding Domain; Dehydroepiandrosterone; Enzalutamide (MDV3100); FDA; Food and Drug Administration; H; Heat Shock Protein; Hinge; Hsp; LBD; LHRH; Ligand-Binding Domain; Luteinizing Hormone-Releasing Hormone; N-Terminal Domain; NSAA; NTD; Non-Steroidal Anti-Androgens; PCa; PSA; Prostate; Prostate Cancer; Prostate-Specific Antigen; RT; Radiation Therapy; Steroidogenesis; TMPRSS2; Transmembrane Protease Serine 2; UGM; Urogenital Sinus Mesenchyme.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

MeSH terms