Androgen Receptor Splice Variant, AR-V7, as a Biomarker of Resistance to Androgen Axis-Targeted Therapies in Advanced Prostate Cancer.

Journal Article (Journal Article;Review)

Many therapeutic options are now available for men with metastatic castration-resistant prostate cancer (mCRPC), including next-generation androgen receptor axis-targeted therapies (AATTs), immunotherapy, chemotherapy, and radioisotope therapies. No clear consensus has been reached for the optimal sequencing of treatments for patients with mCRPC, and few well-validated molecular markers exist to guide the treatment decisions for individual patients. The androgen receptor splice variant 7 (AR-V7), a splice variant of the androgen receptor mRNA resulting in the truncation of the ligand-binding domain, has emerged as a biomarker for resistance to AATT. AR-V7 expression in circulating tumor cells has been associated with poor outcomes in patients treated with second- and third-line AATTs. Clinically validated assays are now commercially available for the AR-V7 biomarker. In the present review of the current literature, we have summarized the biology of resistance to AATT, with a focus on the AR-V7; and the clinical studies that have validated AR-V7 expression as a strong independent predictor of a lack of clinical benefit from AATTs. Existing evidence has indicated that patients with AR-V7-positive mCRPC will have better outcomes if treated with taxane chemotherapy regimens rather than additional AATTs.

Full Text

Duke Authors

Cited Authors

  • Zhang, T; Karsh, LI; Nissenblatt, MJ; Canfield, SE

Published Date

  • February 2020

Published In

Volume / Issue

  • 18 / 1

Start / End Page

  • 1 - 10

PubMed ID

  • 31653572

Electronic International Standard Serial Number (EISSN)

  • 1938-0682

Digital Object Identifier (DOI)

  • 10.1016/j.clgc.2019.09.015

Language

  • eng

Conference Location

  • United States