开发第二代抗雄激素,用于治疗晚期前列腺癌
Chris Tran1, Samedy Ouk, Nicola J Clegg
1Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Science (New York, N.Y.)
|April 11, 2009
概括
新的抗雄激素化合物RD162和MDV3100有效治疗晚期前列腺癌. 它们通过抑制雄激素受体活性来向抵抗割的前列腺癌,在临床前和早期临床研究中显示出有希望的结果.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 由于抵抗机制,转移性前列腺癌的治疗往往会失败.
- 化抵抗性前列腺癌 (CRPC) 是由受体 (AR) 表达率升高所驱动的.
- 现有的抗雄激素疗法对CRPC变得无效.
研究的目的:
- 为了描述新的非类固醇抗雄激素,RD162和MDV3100.
- 在CRPC的临床前模型中评估它们的疗效.
- 在I/II期临床试验中评估它们的安全性和初步疗效.
主要方法:
- 化合物RD162和MDV3100从对非类固醇抗雄激素的选中进行了优化.
- 评估了AR结合亲和力,核转位,DNA结合和协活性剂招募.
- 在体内有效性在CRPC的小鼠模型中进行了测试.
- 进行了一项I/II期临床试验,以评估MDV3100在晚期前列腺癌患者中.
主要成果:
- RD162和MDV3100表现出比双胺更高的AR结合亲和力.
- 这两种化合物都抑制了AR核转位,DNA结合和协活性剂招募.
- 在CRPC小鼠模型中,RD162和MDV3100诱导了瘤回归.
- 在临床试验中,接受MDV3100治疗的43%的患者表现出明显的前列腺特异抗原 (PSA) 减少.
结论:
- RD162和MDV3100是强大的非类固醇抗雄激素,对CRPC有活性.
- 这些化合物代表了晚期前列腺癌的有希望的治疗候选者.
- MDV3100需要在更大的临床试验中对CRPC治疗进行进一步的研究.
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