TY - JOUR
T1 - Androgen Receptor Splice Variant, AR-V7, as a Biomarker of Resistance to Androgen Axis-Targeted Therapies in Advanced Prostate Cancer
AU - Zhang, Tian
AU - Karsh, Lawrence I.
AU - Nissenblatt, Michael J.
AU - Canfield, Steven E.
N1 - Funding Information:
Writing support for our report was provided by H. Jeffrey Lawrence, MD (a former employee of Genomic Health), and editorial and graphics support were provided by Penny Baron at Ashfield Healthcare Communications, and funded by Genomic Health , Inc, Redwood City, CA. The authors would like to acknowledge John Hornberger, MD, an employee of Genomic Health, Inc, for his invaluable help in providing cost data.
Publisher Copyright:
© 2019 The Authors
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Antineoplastic
KW - Drug resistance
KW - Hormonal agents
KW - Metastases
KW - Predictive genomic testing
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U2 - 10.1016/j.clgc.2019.09.015
DO - 10.1016/j.clgc.2019.09.015
M3 - Review article
C2 - 31653572
AN - SCOPUS:85073975608
SN - 1558-7673
VL - 18
SP - 1
EP - 10
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 1
ER -