Capper Cameron P, Rae James M, Auchus Richard J
Division of Hematology/Oncology, Department of Internal Medicine and Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48019, USA.
Division of Metabolism, Diabetes, and Endocrinology, Department of Internal Medicine and Department of Pharmacology, University of Michigan School of Medicine, Room 5560A, MSRBII, 1150 W. Medical Center Drive, Ann Arbor, MI, 48019, USA.
Horm Cancer. 2016 Jun;7(3):149-64. doi: 10.1007/s12672-016-0259-0. Epub 2016 Mar 11.
Breast and prostate cancers are malignancies in which steroid hormones drive cellular proliferation. Over the past century, this understanding has led to successful treatment strategies aimed to inhibit hormone-mediated tumor growth. Nonetheless, disease relapse and progression still pose significant clinical problems, with recurrent and metastatic tumors often exhibiting resistance to current drug therapies. The central role of androgens and estrogens in prostate and breast cancer etiology explains not only why endocrine therapies are often initially successful but also why many tumors ultimately become resistant. It is hypothesized that reducing the concentration of active hormones in the systemic circulation may be insufficient to block cancer progression, as this action selects for tumor cells that can generate active steroids from circulating precursors. This review aims to highlight the currently known differences of steroid biosynthesis in normal physiology versus hormone-dependent cancers, modern approaches to the assessment and targeting of these pathways, and priorities for future research.
乳腺癌和前列腺癌是类固醇激素驱动细胞增殖的恶性肿瘤。在过去的一个世纪里,这一认识催生了旨在抑制激素介导的肿瘤生长的成功治疗策略。尽管如此,疾病复发和进展仍然构成重大的临床问题,复发和转移性肿瘤通常对当前的药物治疗表现出抗性。雄激素和雌激素在前列腺癌和乳腺癌病因中的核心作用不仅解释了内分泌疗法为何常常最初取得成功,也解释了为何许多肿瘤最终会产生抗性。据推测,降低全身循环中活性激素的浓度可能不足以阻止癌症进展,因为这种作用会选择那些能够从循环前体生成活性类固醇的肿瘤细胞。本综述旨在强调目前已知的正常生理学与激素依赖性癌症中类固醇生物合成的差异、评估和靶向这些途径的现代方法以及未来研究的重点。