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The 5,6‐epoxycholesterol metabolic pathway in breast cancer: Emergence of new pharmacological targets

Abstract : Metabolic pathways have emerged as cornerstones in carcinogenic deregulation providing new therapeutic strategies for cancer management. Recently, a new branch of cholesterol metabolism has been discovered involving the biochemical transformation of 5,6-epoxycholesterols (5,6-ECs). The 5,6-ECs are metabolized in breast cancers to the tumour promoter oncosterone whereas, in normal breast tissue, they are metabolized to the tumour suppressor metabolite, dendrogenin A (DDA). Blocking the mitogenic and invasive potential of oncosterone will present new opportunities for breast cancer treatment. The reactivation of DDA biosynthesis, or its use as a drug, represents promising therapeutic approaches such as DDA-deficiency complementation, activation of breast cancer cell re-differentiation and breast cancer chemoprevention. This review presents current knowledge of the 5,6-EC metabolic pathway in breast cancer, focusing on the 5,6-EC metabolic enzymes ChEH and HSD11B2 and on 5,6-EC metabolite targets, the oxysterol receptor (LXRβ) and the glucocorticoid receptor. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit
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https://www.hal.inserm.fr/inserm-03394464
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Submitted on : Friday, October 22, 2021 - 9:49:04 AM
Last modification on : Wednesday, October 27, 2021 - 3:01:03 AM

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Philippe Medina, Khadijetou Diallo, Emilie Huc‐claustre, Mehdi Attia, Régis Soulès, et al.. The 5,6‐epoxycholesterol metabolic pathway in breast cancer: Emergence of new pharmacological targets. British Journal of Pharmacology, Wiley, 2021, 178 (16), pp.3248-3260. ⟨10.1111/bph.15205⟩. ⟨inserm-03394464⟩

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