The development of abiraterone acetate for castration-resistant prostate cancer
The development of abiraterone acetate for castration-resistant prostate cancer
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DOI：
10.1016/j.urolonc.2015.03.021
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发表时间：
2015-06-01
影响因子：
2.7
通讯作者：
Attard, Gerhardt
中科院分区：
文献类型：
--
作者：
Grist, Emily;Attard, Gerhardt
醋酸阿比特龙是一种新型的CYP17A1抑制剂，被证明可以延长去势抵抗性前列腺癌（CRPC）的生存期。本综述探讨了醋酸阿比特龙近20年的发展历史中的关键阶段，从伦敦癌症研究所的一个旨在开发雄激素合成抑制剂的项目开始。由于支持靶向雄激素合成作为CRPC治疗方法的数据不足以及皮质醇抑制导致肾上腺皮质功能不全的安全性问题，临床开发最初进展缓慢。监管机构于2011年批准了醋酸阿比特龙，因为在接受紫杉醇治疗的男性中，与泼尼松单独给药相比，醋酸阿比特龙与泼尼松联合给药具有生存获益。2012年，在放射学无进展生存期显著增加后，许可证批准扩展到包括未经化疗的CRPC患者。正在进行的研究重点是确定预测性生物标志物和了解耐药性机制，以改善其管理。(C)2015 Elsevier Inc. All rights reserved.
Abiraterone acetate is a novel CYP17A1 inhibitor demonstrated to prolong survival in castration-resistant prostate cancer (CRPC). This review explores key stages in the almost 20-year history of abiraterone acetate's development, starting with a program aiming to develop inhibitors of androgen synthesis at the Institute of Cancer Research, London. Clinical development was initially slow owing to insufficient data supporting targeting of androgen synthesis as a therapeutic approach in CRPC and safety concerns of adrenocortical insufficiency from suppression of cortisol. Regulatory authorities approved abiraterone acetate in 2011 after a survival benefit was demonstrated when given in combination with prednisone as compared with prednisone alone in docetaxel-treated men. Licensing approval extended to include chemotherapy-naive patients with CRPC in 2012 following a significant increase in radiographic progression-free survival. Ongoing research focuses on identifying predictive biomarkers and understanding mechanisms of resistance to improve its administration. (C) 2015 Elsevier Inc. All rights reserved.