Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.
Mol Cell Endocrinol. 2012 Sep 5;360(1-2):68-75. doi: 10.1016/j.mce.2011.09.038. Epub 2011 Oct 1.
Patients with advanced prostate cancer initially respond very well to medical or surgical castration. Despite a good initial response, the disease progresses to a castration-resistant state. Castration-resistant prostate cancer (CRPC) remains addicted to androgen receptor signaling. The addition of conventional anti-androgen agents, such as bicalutamide, only provides a transient benefit. This has led to a search for further drug targets. Cytochrome P450 17 (CYP17) is an enzyme that is vital for the adrenal biosynthesis of androgens. The CYP17 inhibitor abiraterone acetate has a proven benefit in a phase III randomized trial and other CYP17 inhibitors are currently being evaluated. The novel antiandrogen MDV3100 is a small molecule androgen receptor antagonist with promising activity. Heat shock proteins (HSPs) bind to the androgen receptor and modify its activity. Several HSP inhibitors are under evaluation in clinical trials. This review explores the role of CYP17 inhibitors, MDV3100, and HSP inhibitors.
患有晚期前列腺癌的患者最初对医学或手术去势治疗反应非常好。尽管初始反应良好，但疾病会发展为去势抵抗状态。去势抵抗性前列腺癌（CRPC）仍然依赖于雄激素受体信号。添加常规抗雄激素药物，如比卡鲁胺，仅提供短暂的益处。这导致了对进一步药物靶点的探索。细胞色素 P450 17（CYP17）是一种对于肾上腺雄激素生物合成至关重要的酶。CYP17 抑制剂阿比特龙醋酸酯在一项 III 期随机试验中具有已证实的益处，其他 CYP17 抑制剂目前正在评估中。新型抗雄激素药物 MDV3100 是一种具有前景的小分子雄激素受体拮抗剂。热休克蛋白（HSPs）与雄激素受体结合并改变其活性。几种 HSP 抑制剂正在临床试验中进行评估。这篇综述探讨了 CYP17 抑制剂、MDV3100 和 HSP 抑制剂的作用。
