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.
Clinical genitourinary cancer. 2019 Sep 26 [Epub ahead of print]
Tian Zhang, Lawrence I Karsh, Michael J Nissenblatt, Steven E Canfield
Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University School of Medicine, Durham, NC. Electronic address: ., The Urology Center of Colorado, Denver, CO., Department of Medicine, Regional Cancer Care Associates and Robert Wood Johnson University Medical School, East Brunswick, NJ., Department of Surgery, University of Texas McGovern Medical School, Houston, TX.