Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer
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...
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Medknow Publications & Media Pvt Ltd
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955182/ |
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pubmed-49551822016-07-26 Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer Luo, Jun Invited Review 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. Medknow Publications & Media Pvt Ltd 2016 2016-05-13 /pmc/articles/PMC4955182/ /pubmed/27174161 http://dx.doi.org/10.4103/1008-682X.178490 Text en Copyright: © Asian Journal of Andrology http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Luo, Jun |
| spellingShingle |
Luo, Jun Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer |
| author_facet |
Luo, Jun |
| author_sort |
Luo, Jun |
| title |
Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer |
| title_short |
Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer |
| title_full |
Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer |
| title_fullStr |
Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer |
| title_full_unstemmed |
Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer |
| title_sort |
development of ar-v7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer |
| description |
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. |
| publisher |
Medknow Publications & Media Pvt Ltd |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955182/ |
| _version_ |
1613612722565414912 |