Androgen receptor variant-driven prostate cancer

  • Antonarakis E
  • Armstrong A
  • Dehm S
  • et al.
ISSN: 1365-7852
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Abstract

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 NH 2 -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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APA

Antonarakis, E. S., Armstrong, A. J., Dehm, S. M., & Luo, J. (2016). Androgen receptor variant-driven prostate cancer. Prostate Cancer and Prostatic Diseases, 19(3), 231–241. Retrieved from https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84981738927&origin=inward

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