There is an emerging interest in understanding mechanisms of response and resistance to next-generation hormonal therapies: abiraterone and enzalutamide. While many explanations for resistance to these agents have been postulated, the importance of androgen receptor splice variants is gaining momentum. Androgen receptor (AR) splice variants are constitutively active isoforms of the AR that lack the ligand-binding domain yet retain their transcriptional activity in a ligand-independent fashion. Of these, AR variant-7 may be the most important, and has been implicated in primary resistance to abiraterone and enzalutamide in men with advanced prostate cancer. In this editorial, the clinical relevance of AR splice variant-7 (AR-V7) will be reviewed within the context of AR-directed therapies, and next steps for the analytical and clinical validation of this potential biomarker will be proposed.
Bibliographical noteFunding Information:
This study was partially funded by NIH Grant P30 CA006973 and by the Prostate Cancer Foundation (PCF). ES Antonarakis has served as a paid consultant/advisor to Janssen, Astellas, Sanofi and Dendreon. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
© 2014 Informa UK, Ltd.
- androgen receptor
- splice variant