Androgen receptor variant-driven prostate cancer: clinical implications and therapeutic targeting.

Journal Article (Review)

While there are myriad mechanisms of primary and acquired resistance to conventional and next-generation hormonal therapies in prostate cancer, the potential role of androgen receptor splice variants (AR-Vs) has recently gained momentum. AR-Vs are abnormally truncated isoforms of the androgen receptor (AR) protein that lack the COOH-terminal domain but retain the NH2-terminal domain and DNA-binding domain and are thus constitutively active even in the absence of ligands. Although multiple preclinical studies have previously implicated AR-Vs in the development of castration resistance as well as resistance to abiraterone and enzalutamide, recent technological advances have made it possible to reliably detect and quantify AR-Vs from human clinical tumor specimens including blood samples. Initial clinical studies have now shown that certain AR-Vs, in particular AR-V7, may be associated with resistance to abiraterone and enzalutamide but not taxane chemotherapies when detected in circulating tumor cells. Efforts are now underway to clinically validate AR-V7 as a relevant treatment-selection biomarker in the context of other key genomic aberrations in men with metastatic castration-resistant prostate cancer. Additional efforts are underway to therapeutically target both AR and AR-Vs either directly or indirectly. Whether AR-Vs represent drivers of castration-resistant prostate cancer, or whether they are simply passenger events associated with aggressive disease or clonal heterogeneity, will ultimately be answered only through these types of clinical trials.

Full Text

Duke Authors

Cited Authors

  • Antonarakis, ES; Armstrong, AJ; Dehm, SM; Luo, J

Published Date

  • September 2016

Published In

Volume / Issue

  • 19 / 3

Start / End Page

  • 231 - 241

PubMed ID

  • 27184811

Electronic International Standard Serial Number (EISSN)

  • 1476-5608

International Standard Serial Number (ISSN)

  • 1365-7852

Digital Object Identifier (DOI)

  • 10.1038/pcan.2016.17

Language

  • eng