Hormones and Cancer

, Volume 5, Issue 5, pp 265–273

Androgen Receptor Splice Variants in the Era of Enzalutamide and Abiraterone


DOI: 10.1007/s12672-014-0190-1

Cite this article as:
Nakazawa, M., Antonarakis, E.S. & Luo, J. HORM CANC (2014) 5: 265. doi:10.1007/s12672-014-0190-1


The FDA approvals of enzalutamide and abiraterone have rapidly changed the clinical landscape of prostate cancer treatment. Both drugs were designed to further suppress androgen receptor (AR) signaling, which is restored following first-line androgen deprivation therapies. Resistance to enzalutamide and abiraterone, however, is again marked by a return of AR signaling, indicating a remarkable “addiction” of prostate cancer cells to the AR pathway. Several mechanisms of castration resistance have been uncovered in the past decades, featuring a wide spectrum of molecular alterations that may explain sustained AR signaling in castration-resistant prostate cancers (CRPC). Among these, the androgen receptor splice variants (AR-Vs), particularly variant 7 (AR-V7), have been implicated in resistance to enzalutamide and abiraterone in preclinical studies, and they cannot be targeted by currently available AR-directed drugs. Drug development for AR-V-associated CRPC may therefore be necessary to augment the preexisting treatment repertoire. In this mini-review, we will discuss general mechanisms of resistance to AR-directed therapies, with a focus on the role of androgen receptor splice variants in the new era of treating advanced prostate cancer with enzalutamide and abiraterone.

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Mary Nakazawa
    • 1
  • Emmanuel S. Antonarakis
    • 2
  • Jun Luo
    • 1
  1. 1.The James Buchanan Brady Urological Institute and Department of UrologyThe Johns Hopkins School of MedicineBaltimoreUSA
  2. 2.Department of OncologyThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreUSA

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