Section of EndocrinologyDepartment of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Institute of Metabolism and Systems ResearchUniversity of Birmingham, Birmingham, UK.
Endocr Relat Cancer. 2017 Nov;24(11):R403-R420. doi: 10.1530/ERC-17-0155. Epub 2017 Sep 18.
Steroid hormones play a central role in the maintenance and progression of prostate cancer. The androgen receptor is the primary driver of tumor cell proliferation and is activated by the androgens testosterone and 5α-dihydrotestosterone. Inhibition of this pathway through medical or surgical castration improves survival in the majority of advanced prostate cancer patients. However, conversion of adrenal androgen precursors and alternative steroidogenic pathways have been found to contribute to tumor progression and resistance to treatment. The emergence of highly accurate detection methods allows us to study steroidogenic mechanisms in more detail, even after treatment with potent steroidogenic inhibitors such as the CYP17A1 inhibitor abiraterone. A clear overview of steroid hormone levels in patients throughout the local, metastatic and castration-resistant stages of prostate cancer and treatment modalities is key toward a better understanding of their role in tumor progression and treatment resistance. In this review, we summarize the currently available data on steroid hormones that have been implicated in the various stages of prostate cancer. Additionally, this review addresses the implications of these findings, highlights important studies in this field and identifies current gaps in literature.
甾体激素在前列腺癌的维持和进展中发挥着核心作用。雄激素受体是肿瘤细胞增殖的主要驱动因素,它被雄激素睾酮和 5α-二氢睾酮激活。通过医学或手术去势抑制这条途径,可改善大多数晚期前列腺癌患者的生存率。然而,已经发现肾上腺雄激素前体和替代的甾体生成途径的转化会导致肿瘤进展和对治疗的耐药。高度准确的检测方法的出现使我们能够更详细地研究甾体生成机制,即使在使用强效甾体生成抑制剂(如 CYP17A1 抑制剂阿比特龙)治疗后也是如此。全面了解前列腺癌患者在局部、转移性和去势抵抗性阶段以及治疗方式的甾体激素水平,对于更好地理解它们在肿瘤进展和治疗耐药性中的作用至关重要。在这篇综述中,我们总结了目前关于与前列腺癌各个阶段相关的甾体激素的可用数据。此外,本综述还探讨了这些发现的意义,强调了该领域的重要研究,并确定了目前文献中的空白。