Oxygenation products of cholesterol, named oxysterols, were suspected since the 20^th century to be involved in carcinogenesis. Among the family of oxysterol molecules, cholesterol-5,6-epoxides (5,6-EC) retained the attention of scientists because they contain a putative alkylating epoxide group. However, studies failed into demonstrating that 5,6-EC were direct carcinogens and revealed a surprising chemical stability and unreactivity towards nucleophiles in standard conditions. Analyses of 5,6-EC metabolism in normal cells showed that they were extensively transformed into cholestane-3β,5α,6β-triol (CT) by the cholesterol-5,6-epoxide hydrolase (ChEH). Studies performed in cancer cells showed that CT was additionally metabolized into an oxysterol identified as the 6-oxo-cholestan-3β,5α-diol (OCDO), by the 11β-hydroxysteroid dehydrogenase of type 2 (HSD2), the enzyme which inactivates cortisol into cortisone. Importantly, OCDO was shown to display tumor promoter properties in breast cancers, by binding to the glucocorticoid receptor, and independently of their estrogen receptor status, revealing the existence of a new tumorigenic pathway centered on 5,6-EC. In breast tumors from patients, OCDO production as well as the expression of the enzymes involved in the pathway producing OCDO, namely ChEH subunits and HSD2, were higher compared to normal tissues, and overexpression of these enzymes correlate with a higher risk of patient death, indicating that this onco-metabolism is of major importance to breast cancer pathology. Herein, we will review the actual knowledge and the future trends in OCDO chemistry, biochemistry, metabolism and mechanism of action and will discuss the impact of OCDO discovery on new anticancer therapeutic strategies.

氧化产物胆固醇，名叫氧固醇，是因为怀疑20^日参与致癌的世纪。在氧固醇分子家族中，胆固醇5,6-环氧化物（5,6-EC）引起了科学家的注意，因为它们含有一个推定的烷基化环氧化物基团。然而，研究未能证明5，6-EC是直接致癌物，并显示出令人惊讶的化学稳定性和在标准条件下对亲核试剂无反应性。对正常细胞中5,6-EC代谢的分析表明，它们被胆固醇-5,6-环氧化物水解酶（ChEH）广泛转化为胆固醇3β，5α，6β-三醇（CT）。在癌细胞中进行的研究表明，CT还通过2型11β-羟基类固醇脱氢酶（HSD2）被代谢为被确定为6-氧代胆甾醇3β，5α-二醇（OCDO）的氧固醇。进入可的松。重要的，OCDO通过与糖皮质激素受体结合而显示出在乳腺癌中的肿瘤启动子特性，并且独立于它们的雌激素受体状态，揭示了以5，6-EC为中心的新致瘤途径的存在。在来自患者的乳腺肿瘤中，与正常组织相比，OCDO的产生以及与产生OCDO的途径有关的酶（即ChEH亚基和HSD2）的表达均高于正常组织，并且这些酶的过表达与患者死亡的风险更高相关，这表明这种癌代谢对乳腺癌病理学至关重要。在这里，我们将回顾OCDO化学，生物化学，新陈代谢和作用机理的实际知识和未来趋势，并讨论OCDO发现对新抗癌治疗策略的影响。