Snaterse Gido, Hofland Johannes, Lapauw Bruno
Department of Endocrinology and Metabolism, Ghent University Hospital, Ghent, Belgium.
Section of Endocrinology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Endocr Oncol. 2023 Mar 13;3(1):e220072. doi: 10.1530/EO-22-0072. eCollection 2023 Jan 1.
11-oxygenated androgens are a class of steroids capable of activating the androgen receptor (AR) at physiologically relevant concentrations. In view of the AR as a key driver of prostate cancer (PC), these steroids are potential drivers of disease and progression. The 11-oxygenated androgens are adrenal-derived, and persist after androgen deprivation therapy (ADT), the mainstay treatment for advanced PC. Consequently, these steroids are of particular interest in the castration-resistant prostate cancer (CRPC) setting. The principal androgen of the pathway, 11-ketotestosterone (11KT), is a potent AR agonist and the predominant circulating active androgen in CRPC patients. Additionally, several precursor steroids are present in the circulation which can be converted into active androgens by steroidogenic enzymes present in PC cells. evidence suggests that adaptations frequently observed in CRPC favour the intratumoral accumulation of 11-oxygenated androgens in particular. Still, apparent gaps in our understanding of the physiology and role of the 11-oxygenated androgens remain. In particular, and clinical evidence supporting these findings is limited. Despite recent advances, a comprehensive assessment of intratumoral concentrations has not yet been performed. The exact contribution of the 11-oxygenated androgens to CRPC progression therefore remains unclear. This review will focus on the current evidence linking the 11-oxygenated androgens to PC, will highlight current gaps in our knowledge, and will provide insight into the potential clinical importance of the 11-oxygenated androgens in the CRPC setting based on the current evidence.
11-氧化雄激素是一类在生理相关浓度下能够激活雄激素受体（AR）的类固醇。鉴于AR是前列腺癌（PC）的关键驱动因素，这些类固醇是疾病和进展的潜在驱动因素。11-氧化雄激素源自肾上腺，在雄激素剥夺疗法（ADT）（晚期PC的主要治疗方法）后仍会持续存在。因此，这些类固醇在去势抵抗性前列腺癌（CRPC）环境中特别受关注。该途径的主要雄激素11-酮睾酮（11KT）是一种强效AR激动剂，也是CRPC患者中主要的循环活性雄激素。此外，循环中存在几种前体类固醇，它们可被PC细胞中存在的类固醇生成酶转化为活性雄激素。有证据表明，CRPC中常见的适应性变化尤其有利于11-氧化雄激素在肿瘤内的积累。尽管如此，我们对11-氧化雄激素的生理学和作用的理解仍存在明显差距。特别是，支持这些发现的临床证据有限。尽管最近取得了进展，但尚未对肿瘤内浓度进行全面评估。因此，11-氧化雄激素对CRPC进展的确切贡献仍不清楚。本综述将聚焦于将11-氧化雄激素与PC联系起来的现有证据，突出我们目前知识上的差距，并根据现有证据深入探讨11-氧化雄激素在CRPC环境中的潜在临床重要性。
