Androgen receptor as a target in androgen-independent prostate cancer
Androgen receptor as a target in androgen-independent prostate cancer
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DOI：
10.1016/s0090-4295(02)01593-5
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发表时间：
2002-09-01
期刊：
影响因子：
2.1
通讯作者：
Balk, SP
中科院分区：
文献类型：
--
作者：
Balk, SP
前列腺癌依赖于由雄激素受体（AR）介导的雄激素刺激，雄激素受体是配体依赖性核受体的类固醇激素受体家族的成员。大多数患者对标准雄激素消融治疗有反应，但几乎所有患者最终都会复发，这些疾病被称为雄激素难治性或雄激素非依赖性疾病。使用AR拮抗剂（如氟鲁胺或比卡鲁胺）来增强对原发性雄激素消融治疗的反应或治疗雄激素非依赖性前列腺癌的努力令人失望，这降低了对更积极或替代方法阻断AR功能的热情。然而，许多证据表明，AR功能有助于雄激素消融后肿瘤细胞的存活和雄激素非依赖性前列腺癌的生长。本文概述了一些可能有助于雄激素非依赖性前列腺癌中AIR活性的机制，包括AIR扩增、AIR突变、AIR辅激活子和辅阻遏蛋白表达改变以及其他可增强AIR功能的途径的激活。了解雄激素非依赖性前列腺癌中AR功能的机制，应允许更合理地开发可增强雄激素消融治疗疗效的拮抗剂。
Prostate cancer is dependent on androgen stimulation mediated by the androgen receptor (AR), a member of the steroid hormone receptor family of ligand-dependent nuclear receptors. Most patients respond to standard androgen ablation therapies, but virtually all patients eventually relapse with disease that has been termed hormone-refractory or androgen-independent disease. Efforts to use AR antagonists, such as flutamide or bicalutamide, to enhance responses to primary androgen ablation therapy or to treat androgen-independent prostate cancer have been disappointing, which has diminished enthusiasm for more aggressive or alternative methods to block AR function. However, many lines of evidence indicate that AR function contributes to tumor cell survival after androgen ablation and to growth of androgen-independent prostate cancer. This article outlines a number of mechanisms that may contribute to AIR activity in androgen-independent prostate cancer, including AIR amplification, AIR mutation, altered expression of AIR coactivator and corepressor proteins, and activation of other pathways that can enhance AIR function. Understanding the mechanisms responsible for AR function in androgen-independent prostate cancer should allow the more rational development of antagonists that can enhance the efficacy of androgen ablation therapies.