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

Tian Zhang, Lawrence I. Karsh, Michael J. Nissenblatt, Steven E. Canfield

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalClinical Genitourinary Cancer
Volume18
Issue number1
DOIs
StatePublished - Feb 2020
Externally publishedYes

Keywords

  • Antineoplastic
  • Drug resistance
  • Hormonal agents
  • Metastases
  • Predictive genomic testing

ASJC Scopus subject areas

  • Oncology
  • Urology

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