Strategies for targeting the androgen receptor axis in prostate

Drug discovery today · Sep 2014

Review

Strategies for targeting the androgen receptor axis in prostate cancer.

Androgen receptor (AR) signaling plays a critical role in prostate cancer cell proliferation, survival, and differentiation. Therapeutic strategies targeting the androgen receptor have been developed for the treatment of metastatic hormone-naïve prostate cancer; however, despite effective targeting recent studies have demonstrated that during progression to a castrate-resistant phenotype there is restoration of AR target gene expression. On the basis of this observation, second-generation therapeutics have been developed to target AR in the castrate-resistant setting resulting in a survival benefit. In this review we will discuss the mechanisms promoting AR signaling and the development of second-generation therapeutics targeting AR in castrate-resistant prostate cancer.

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- Brett S Carver.
- Department of Surgery, Division of Urology and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address: carverb@mskcc.org.
- Drug Discov. Today. 2014 Sep 1; 19 (9): 1493-7.
AbstractAndrogen receptor (AR) signaling plays a critical role in prostate cancer cell proliferation, survival, and differentiation. Therapeutic strategies targeting the androgen receptor have been developed for the treatment of metastatic hormone-naïve prostate cancer; however, despite effective targeting recent studies have demonstrated that during progression to a castrate-resistant phenotype there is restoration of AR target gene expression. On the basis of this observation, second-generation therapeutics have been developed to target AR in the castrate-resistant setting resulting in a survival benefit. In this review we will discuss the mechanisms promoting AR signaling and the development of second-generation therapeutics targeting AR in castrate-resistant prostate cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Strategies for targeting the androgen receptor axis in prostate cancer.

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