Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
J Investig Med. 2012 Feb;60(2):495-503. doi: 10.2310/JIM.0b013e3182408567.
In 2005, results from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial ushered in a new era of endocrine therapy for hormone-responsive malignancies. This study demonstrated that, compared with tamoxifen (a selective estrogen receptor modulator), anastrozole (aromatase inhibitor [AI]) prolonged time to recurrence and disease-free survival for postmenopausal women with breast cancer. The advantage was even greater for those with estrogen receptor-positive (ER) tumors, and anastrozole was better tolerated than tamoxifen. Since then, AIs have become first-line adjuvant therapy for ER breast cancer in postmenopausal women.In late 2010, a trial comparing abiraterone acetate (a 17-hydroxylase/17,20-lyase [CYP17A1] inhibitor) plus prednisone versus prednisone alone in men with castration-resistant prostate cancer (CRPC) previously treated with docetaxel chemotherapy was terminated early because of the survival benefit in the abiraterone acetate arm. This result not only validated a new therapy for CRPC but also, with the antecedent phase I-II abiraterone studies, shattered our understanding of the molecular mechanisms underpinning CRPC development and progression.Aromatase inhibitors and CYP17A1 inhibitors will be widely used by oncologists, yet fellowship programs provide little training in steroid biosynthesis, compared with training in the biology of standard chemotherapies. Consequently, these drugs might be used without an appreciation of their caveats and pitfalls. The purpose of this review was to acquaint practicing oncologists with the fundamental principles and pathways of steroid biosynthesis, to improve their understanding of how and why these drugs work, and to alert these physicians to potential problems related to the drugs' mechanisms of action.
2005 年，阿那曲唑、他莫昔芬单药或联合治疗（ATAC）试验的结果开创了激素反应性恶性肿瘤内分泌治疗的新纪元。该研究表明，与他莫昔芬（一种选择性雌激素受体调节剂）相比，阿那曲唑（芳香化酶抑制剂 [AI]）延长了绝经后乳腺癌患者的复发时间和无病生存期。对于雌激素受体阳性（ER）肿瘤患者，优势更为明显，而且阿那曲唑的耐受性优于他莫昔芬。从那时起，AI 已成为绝经后 ER 阳性乳腺癌的一线辅助治疗药物。
2010 年末，一项比较醋酸阿比特龙（一种 17-羟化酶/17,20-裂合酶 [CYP17A1]抑制剂）加泼尼松与单独使用泼尼松治疗先前接受多西他赛化疗的去势抵抗性前列腺癌（CRPC）男性的试验因阿比特龙组的生存获益而提前终止。这一结果不仅验证了一种新的 CRPC 治疗方法，而且通过先前的 I-II 期阿比特龙研究，打破了我们对 CRPC 发展和进展的分子机制的理解。
芳香化酶抑制剂和 CYP17A1 抑制剂将被肿瘤学家广泛使用，但与标准化疗的生物学培训相比，奖学金计划在类固醇生物合成方面提供的培训较少。因此，这些药物可能在没有充分认识到其注意事项和陷阱的情况下使用。本综述的目的是使临床肿瘤学家了解类固醇生物合成的基本原理和途径，提高他们对这些药物如何以及为何起作用的理解，并提醒这些医生注意与这些药物作用机制相关的潜在问题。
