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

Publication ,  Journal Article
Antonarakis, ES; Armstrong, AJ; Dehm, SM; Luo, J
Published in: Prostate Cancer Prostatic Dis
September 2016

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.

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Published In

Prostate Cancer Prostatic Dis

DOI

EISSN

1476-5608

Publication Date

September 2016

Volume

19

Issue

3

Start / End Page

231 / 241

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Treatment Outcome
  • Transcription, Genetic
  • Signal Transduction
  • Research
  • Receptors, Androgen
  • Protein Multimerization
  • Protein Interaction Domains and Motifs
  • Protein Binding
  • Prostatic Neoplasms
 

Citation

APA
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Antonarakis, E. S., Armstrong, A. J., Dehm, S. M., & Luo, J. (2016). Androgen receptor variant-driven prostate cancer: clinical implications and therapeutic targeting. Prostate Cancer Prostatic Dis, 19(3), 231–241. https://doi.org/10.1038/pcan.2016.17
Antonarakis, E. S., A. J. Armstrong, S. M. Dehm, and J. Luo. “Androgen receptor variant-driven prostate cancer: clinical implications and therapeutic targeting.Prostate Cancer Prostatic Dis 19, no. 3 (September 2016): 231–41. https://doi.org/10.1038/pcan.2016.17.
Antonarakis ES, Armstrong AJ, Dehm SM, Luo J. Androgen receptor variant-driven prostate cancer: clinical implications and therapeutic targeting. Prostate Cancer Prostatic Dis. 2016 Sep;19(3):231–41.
Antonarakis, E. S., et al. “Androgen receptor variant-driven prostate cancer: clinical implications and therapeutic targeting.Prostate Cancer Prostatic Dis, vol. 19, no. 3, Sept. 2016, pp. 231–41. Pubmed, doi:10.1038/pcan.2016.17.
Antonarakis ES, Armstrong AJ, Dehm SM, Luo J. Androgen receptor variant-driven prostate cancer: clinical implications and therapeutic targeting. Prostate Cancer Prostatic Dis. 2016 Sep;19(3):231–241.

Published In

Prostate Cancer Prostatic Dis

DOI

EISSN

1476-5608

Publication Date

September 2016

Volume

19

Issue

3

Start / End Page

231 / 241

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Treatment Outcome
  • Transcription, Genetic
  • Signal Transduction
  • Research
  • Receptors, Androgen
  • Protein Multimerization
  • Protein Interaction Domains and Motifs
  • Protein Binding
  • Prostatic Neoplasms