新型雄激素受体拮抗剂治疗去势抵抗性前列腺癌的研究进展

前列腺癌的进展与雄激素受体（ androgen receptor，AR）以及AR反应通路相关，进展期前列腺癌患者需接受雄激素阻断治疗，而去势抵抗性前列腺癌（ castration－resistant prostate cancer，CRPC）的临床治疗更加复杂。 Enz-alutamide，ARN－509，ONC1－13B三种新型AR拮抗剂是用于AR的靶向药物，临床研究正在进行中。 AR拮抗剂效果明显且副作用小，因此应用这一类药物治疗CRPC的方法便日益凸显其重要性。

Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC). Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

转移性前列腺癌治疗药Enzalutamide

雄激素受体拮抗剂 enzalutamide(商品名:Xtandi)于2012年8月31日获美国FDA批准上市,适应证为经多西他赛治疗无效的转移性去势抵抗性前列腺癌(本刊2012年第10期曾报道).该药可作用于雄激素受体信号通路的不同阶段,其可竞争性抑制雄激素与雄激素受体的结合,并抑制雄激素受体的核转位及与DNA的相互作用.Enzalutamide 不但可降低前列腺癌细胞的增殖并诱导其死亡,还能降低前列腺癌荷瘤小鼠的肿瘤体积,其主要代谢产物 N-去甲基化产物的体外活性与本品相近.