The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.
The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.
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DOI：
10.1007/s12672-016-0259-0
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发表时间：
2016-06
影响因子：
3
通讯作者：
Auchus RJ
中科院分区：
文献类型：
--
作者：
Capper CP;Rae JM;Auchus RJ
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。在过去的世纪，这种理解导致了成功的治疗策略，旨在抑制肿瘤细胞介导的肿瘤生长。尽管如此，疾病复发和进展仍然造成重大的临床问题，复发性和转移性肿瘤通常表现出对当前药物治疗的抗性。雄激素和雌激素在前列腺癌和乳腺癌病因学中的核心作用解释了为什么内分泌疗法最初通常是成功的，但也解释了为什么许多肿瘤最终变得耐药。假设降低体循环中活性激素的浓度可能不足以阻断癌症进展，因为这种作用选择可以从循环前体产生活性类固醇的肿瘤细胞。本文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优先事项。
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 cancers etiology explains 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.