Targeting the androgen receptor pathway in prostate cancer.
Targeting the androgen receptor pathway in prostate cancer.
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DOI：
10.1016/j.coph.2008.07.005
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发表时间：
2008-08
影响因子：
4
通讯作者：
Scher, Howard I.
中科院分区：
文献类型：
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作者：
Chen, Yu;Sawyers, Charles L.;Scher, Howard I.
当前列腺癌在雄激素消耗治疗后进展时，目前只有一种治疗选择，即多西他赛，已被证明可以延长生命。最近的研究表明，去势抵抗性前列腺癌（CRPC）继续依赖于雄激素受体（AR）信号，尽管血清雄激素水平低，但雄激素受体（AR）信号仍被重新激活。目前可用的AR靶向治疗，包括GnRH激动剂和抗雄激素，不能完全关闭AR信号。在雄激素缺乏的环境中，增强AR信号的几个机制已经被阐明。这些包括可被低雄激素水平或其他内源性类固醇激活的AR突变、AR过表达、局部内源性雄激素合成增加以及酪氨酸激酶途径上调。这导致了许多针对AR信号通路的新型药物的发展，包括更有效的抗雄激素、CYP17抑制剂（雄激素合成所需的酶）、5α-还原酶抑制剂、保护AR免受降解的HSP90抑制剂、组蛋白去乙酰化酶抑制剂（AR介导的最佳转录所需的组蛋白去乙酰化酶）以及酪氨酸激酶抑制剂。其中许多策略目前正在CRPC的临床试验中进行测试。
When prostate cancers progress following androgen depletion therapy, there are currently few treatment options with only one, docetaxel, that has been shown to prolong life. Recent work has shown that castration resistant prostate cancers (CRPC) continue to depend on androgen receptor (AR) signaling which is reactivated despite low serum androgen levels. Currently available AR targeted therapy, including GnRH agonists and antiandrogens, cannot completely shut down AR signaling. Several mechanisms that enhance AR signaling in an androgen depleted environment have been elucidated. These include AR mutations that allow activation by low androgen levels or by other endogenous steroids, AR overexpression, increased local intracrine synthesis of androgens, and upregulation of tyrosine kinase pathways. This has led to the development of a number of novel agents targeting AR signaling pathway, including more effective antiandrogens, inhibitors of CYP17, an enzyme required for androgen synthesis, inhibitors of 5α-reductase, inhibitors of HSP90 which protects AR from degradation, inhibitors of histone deacetylases which is required for optimal AR mediated transcription, as well as inhibitors of tyrosine kinase inhibitors. Many of these strategies are currently being tested in clinical trials in CRPC.
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影响因子：
5.7
作者：
Marrocco, Deborah L.;Tilley, Wayne D.;Butler, Lisa M.
通讯作者：
Butler, Lisa M.
DOI：
10.1073/pnas.0700420104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Mahajan, Nupam P.;Liu, Yuanbo;Whang, Young E.
通讯作者：
Whang, Young E.
影响因子：
82.9
作者：
Craft, N;Shostak, Y;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
4
作者：
Korkmaz, CG;Fronsdal, K;Saatcioglu, F
通讯作者：
Saatcioglu, F
影响因子：
8.8
作者：
通讯作者：
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