Attard Gerhardt, Reid Alison H M, Olmos David, de Bono Johann S
Section of Medicine, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Cancer Res. 2009 Jun 15;69(12):4937-40. doi: 10.1158/0008-5472.CAN-08-4531. Epub 2009 Jun 9.
Abiraterone acetate is a potent, selective, and orally bioavailable small molecule inhibitor of CYP17, an enzyme that catalyzes two key serial reactions (17 alpha hydroxylase and 17,20 lyase) in androgen and estrogen biosynthesis. Clinical trials have confirmed that specific inhibition of CYP17 is safe and results in clinically important antitumor activity in up to 70% of castrate patients with advanced prostate cancer resistant to currently available endocrine therapies. These clinical data indicate that castration-resistant prostate cancer frequently remains hormone dependent and has confirmed that this disease should no longer be described as "hormone resistant or refractory". Biomarker studies, including the analysis of ETS gene fusion status, on patients treated with abiraterone acetate may allow enrichment of patients with a sensitive phenotype in future studies of therapeutics targeting CYP17.
醋酸阿比特龙是一种强效、选择性且口服生物利用度高的小分子CYP17抑制剂，CYP17是一种在雄激素和雌激素生物合成过程中催化两个关键连续反应（17α羟化酶和17,20裂解酶）的酶。临床试验已证实，对CYP17的特异性抑制是安全的，并且在高达70%对现有内分泌疗法耐药的去势晚期前列腺癌患者中产生临床上重要的抗肿瘤活性。这些临床数据表明，去势抵抗性前列腺癌通常仍依赖激素，并已证实这种疾病不应再被描述为“激素抵抗或难治性”。对接受醋酸阿比特龙治疗的患者进行的生物标志物研究，包括对ETS基因融合状态的分析，可能会在未来针对CYP17的治疗研究中使具有敏感表型的患者得到富集。
