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

Philippe de MedinaKhadijetou DialloEmilie Huc-ClaustreMehdi AttiaRégis SoulèsSandrine Silvente-PoirotMarc Poirot
Published in: British journal of pharmacology (2020)
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 http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.
Keyphrases
  • healthcare
  • dna methylation
  • public health
  • gene expression
  • mental health
  • small molecule
  • childhood cancer
  • young adults
  • risk assessment
  • polycyclic aromatic hydrocarbons
  • health promotion