Department of Medicine, Cleveland Clinic, Cleveland, OH, USA.
Genitourinary Malignancies Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Endocr Rev. 2021 May 25;42(3):354-373. doi: 10.1210/endrev/bnab002.
Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement, from the types of gonadal testosterone deprivation to modalities that block the generation of adrenal and other extragonadal androgens, to those that directly bind and inhibit the androgen receptor (AR). The clinical states of prostate cancer are the product of a superimposition of these therapies with nonmetastatic advanced prostate cancer, as well as frankly metastatic disease. Today's standard of care for advanced prostate cancer includes gonadotropin-releasing hormone agonists (e.g., leuprolide), second-generation nonsteroidal AR antagonists (enzalutamide, apalutamide, and darolutamide) and the androgen biosynthesis inhibitor abiraterone. The purpose of this review is to provide an assessment of hormonal therapies for the various clinical states of prostate cancer. The advancement of today's standard of care will require an accounting of an individual's androgen physiology that also has recently recognized germline determinants of peripheral androgen metabolism, which include HSD3B1 inheritance.
在 20 世纪 40 年代，哈金斯（Huggins）和霍奇斯（Hodges）证实了性腺睾丸酮剥夺的治疗效果，因此牢固地确立了前列腺癌是一种高度依赖雄激素的疾病的概念。从那时起，激素疗法经历了迭代发展，从性腺睾丸酮剥夺的类型到阻断肾上腺和其他性腺外雄激素生成的方式，再到直接结合并抑制雄激素受体（AR）的方式。前列腺癌的临床状态是这些疗法与非转移性晚期前列腺癌以及明显转移性疾病叠加的结果。目前，晚期前列腺癌的标准治疗包括促性腺激素释放激素激动剂（例如亮丙瑞林）、第二代非甾体类 AR 拮抗剂（恩杂鲁胺、阿帕鲁胺和达罗他胺）和雄激素生物合成抑制剂阿比特龙。本文旨在对前列腺癌各种临床状态的激素疗法进行评估。当今标准治疗的进步将需要对个体的雄激素生理学进行评估，最近还认识到外周雄激素代谢的种系决定因素，包括 HSD3B1 遗传。
