Journal
ASIAN JOURNAL OF ANDROLOGY
Volume 18, Issue 4, Pages 580-585Publisher
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1008-682X.178490
Keywords
androgen receptor; androgen receptor splice variant-7 (AR-V7); castration-resistance prostate cancer; circulating tumor cells; treatment selection
Categories
Funding
- Prostate Cancer Foundation
- NIH [R01 CA185297]
- US Department of Defense Prostate Cancer Research Program [W81XWH-13-2-0093, W81XWH-15-2-0050]
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Prostate cancer cells demonstrate a remarkable addiction to androgen receptor (AR) signaling in all stages of disease progression. As such, suppression of AR signaling remains the therapeutic goal in systemic treatment of prostate cancer. A number of molecular alterations arise in patients treated with AR-directed therapies. These molecular alterations may indicate the emergence of treatment resistance and may be targeted for the development of novel agents for prostate cancer. The presence of functional androgen receptor splice variants may represent a potential explanation for resistance to abiraterone and enzalutamide, newer AR-directed agents developed to treat metastatic castration-resistant prostate cancer (mCRPC). In the last 8 years, many androgen receptor splice variants have been identified and characterized. Among these, androgen receptor splice variant-7 (AR-V7) has been investigated extensively. In AR-V7, the entire COOH-terminal ligand-binding domain of the canonical AR is truncated and replaced with a variant-specific peptide of 16 amino acids. Functionally, AR-V7 is capable of mediating constitutive nuclear localization and androgen receptor signaling in the absence of androgens, or in the presence of enzalutamide. In this review, we will focus on clinical translational studies involving detection/measurement of AR-V7. Methods have been developed to detect AR-V7 in clinical mCRPC specimens. AR-V7 can be reliably measured in both tissue and circulating tumor cells derived from mCRPC patients, making it possible to conduct both cross-sectional and longitudinal clinical correlative studies. Current evidence derived from studies focusing on detection of AR-V7 in mCRPC support its potential clinical utility as a treatment selection marker.
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