Emerging data on androgen receptor splice variants in prostate cancer

Endocr Relat Cancer. 2016 Dec;23(12):T199-T210. doi: 10.1530/ERC-16-0298. Epub 2016 Oct 4.

Abstract

Androgen receptor splice variants are alternatively spliced variants of androgen receptor, which are C-terminally truncated and lack the canonical ligand-binding domain. Accumulating evidence has indicated a significant role of androgen receptor splice variants in mediating resistance of castration-resistant prostate cancer to current therapies and in predicting therapeutic responses. As such, there is an urgent need to target androgen receptor splicing variants for more effective treatment of castration-resistant prostate cancer. Identification of precise and critical targeting points to deactivate androgen receptor splicing variants relies on a deep understanding of how they are generated and the mechanisms of their action. In this review, we will focus on the emerging data on their generation, clinical significance and mechanisms of action as well as the therapeutic influence of these findings.

Keywords: androgen receptor; cofactors; dimerization; prostate cancer; splice variant.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Animals
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Protein Isoforms / genetics
  • Receptors, Androgen / genetics*

Substances

  • AR protein, human
  • Protein Isoforms
  • Receptors, Androgen