靶向雄激素受体。

Targeting the androgen receptor.

机构信息

Division of Genitourinary Medical Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.

出版信息

Urol Clin North Am. 2012 Nov;39(4):453-64. doi: 10.1016/j.ucl.2012.07.003.

DOI:10.1016/j.ucl.2012.07.003

PMID:23084523

Abstract

Androgen receptor (AR)-mediated signaling is critical to the growth and survival of prostate cancer. Although medical castration and antiandrogen therapy can decrease AR activity and lower PSA, castration resistance eventually develops. Recent work exploring the molecular structure and evolution of AR in response to hormonal therapies has revealed novel mechanisms of progression of castration-resistant prostate cancer and yielded new targets for drug development. This review focuses on understanding the mechanisms of persistent AR signaling in the castrate environment, and highlights new therapies either currently available or in clinical trials, including androgen synthesis inhibitors and novel direct AR inhibitors.

摘要

雄激素受体 (AR) 介导的信号通路对于前列腺癌的生长和存活至关重要。尽管医学去势和抗雄激素治疗可以降低 AR 活性和 PSA，但最终会出现去势抵抗。最近的研究探索了 AR 的分子结构和进化，以应对激素治疗，揭示了去势抵抗性前列腺癌进展的新机制，并为药物开发提供了新的靶点。本综述重点探讨了在去势环境中持续的 AR 信号转导的机制，并强调了目前可用或正在临床试验中的新疗法，包括雄激素合成抑制剂和新型直接 AR 抑制剂。