Human steroid biosynthesis for the oncologist.
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.
Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
Mary Louise
ML
Auchus
Richard J
RJ
Auchus
D000818:Animals; D053898:Biosynthetic Pathways; D025461:Feedback, Physiological; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D010820:Physicians; D013256:Steroids / Q000096:biosynthesis*
D013256:Steroids