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Discover Oncology
Published in: Discover Oncology 5/2014

01-10-2014 | Review

Androgen Receptor Splice Variants in the Era of Enzalutamide and Abiraterone

Authors: Mary Nakazawa, Emmanuel S. Antonarakis, Jun Luo

Published in: Discover Oncology | Issue 5/2014

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Abstract

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.
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Metadata
Title
Androgen Receptor Splice Variants in the Era of Enzalutamide and Abiraterone
Authors
Mary Nakazawa
Emmanuel S. Antonarakis
Jun Luo
Publication date
01-10-2014
Publisher
Springer US
Published in
Discover Oncology / Issue 5/2014
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-014-0190-1

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