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August 2015

Has the Time Arrived for Biomarker-Directed Therapy in Castration-Resistant Prostate Cancer?

Author Affiliations
  • 1Lank Center of Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • 2Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  • 3Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

Copyright 2015 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Oncol. 2015;1(5):577-579. doi:10.1001/jamaoncol.2015.1457

Men with advanced prostate cancer live for years while receiving sequential cancer treatments that are costly and associated with morbidity. The mainstay of systemic treatment is androgen deprivation therapy aimed at abrogating critical androgen receptor (AR) directed growth, but it invariably leads to the development of castration-resistant prostate cancer (CRPC). There are 7 approved therapies for metastatic CRPC (mCRPC) but no prospective validated data to guide individualized treatment or the sequence of treatments. Many men with CRPC respond to secondary hormonal treatments such as CYP17A1 inhibitors (abiraterone) or to a more potent AR antagonist (enzalutamide), but responses are not durable. One mechanism that contributes to resistance is alternative splicing of the AR to generate AR variants (AR-Vs) that lack the ligand-binding domain and therefore no longer require androgen; AR variant 7 (AR-V7) is the most commonly expressed AR-V.1 Studies evaluating AR-V7 reported by Antonarakis et al first in the context of abiraterone and enzalutamide therapy2 and in this issue of JAMA Oncology3 with taxane therapy provide promise for AR-V7 as the first predictive biomarker in CRPC.