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The 5,6-epoxycholesterol metabolic pathway in cancer: emergence of new pharmacological targets
  • +4
  • Philippe de Medina,
  • Khadijetou Diallo,
  • Emilie Huc-Claustre,
  • Mehdi Attia,
  • Régis Soulès,
  • Sandrine Silvente-Poirot,
  • Marc PoirotOrcid
Philippe de Medina
UMR 1037
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Khadijetou Diallo
UMR 1037
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Emilie Huc-Claustre
UMR 1037
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Mehdi Attia
UMR 1037
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Régis Soulès
Cancer Research Center of Toulouse
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Sandrine Silvente-Poirot
UMR 1037
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Marc Poirot
Orcid
Cancer Research Center of Toulouse
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Peer review status:ACCEPTED

27 May 2020Submitted to British Journal of Pharmacology
28 May 2020Submission Checks Completed
28 May 2020Assigned to Editor
01 Jun 2020Reviewer(s) Assigned
24 Jun 2020Review(s) Completed, Editorial Evaluation Pending
25 Jun 2020Editorial Decision: Revise Minor
06 Jul 20201st Revision Received
08 Jul 2020Submission Checks Completed
08 Jul 2020Assigned to Editor
09 Jul 2020Review(s) Completed, Editorial Evaluation Pending
10 Jul 2020Editorial Decision: Accept

Abstract

Metabolic pathways have emerged as cornerstones in carcinogenic deregulation providing new therapeutic strategies for cancer management. This is illustrated by the recent discovery of a cholesterol metabolic branch involving the biochemical transformation of 5,6-epoxycholesterol (5,6-ECs). 5,6-ECs have been shown to be differentially metabolized in breast cancers (BC) compared to normal breast tissue. 5,6-ECs are metabolized into the tumour promoter oncosterone in BC, while they are transformed into the tumour suppressor metabolite dendrogenin A (DDA) in normal breast tissue. Blocking oncosterone’s mitogenic and invasive potential will represent new opportunities for BC treatment. The reactivation of DDA biosynthesis, or its use as a drug, represents promising therapeutic approaches such as DDA-deficiency complementation, activation of BC cell re-differentiation and BC chemoprevention. This review presents current knowledge as to the 5,6-EC metabolic pathway in BC focusing on the 5,6-EC metabolic enzymes ChEH and HSD11B2, and on 5,6-EC metabolite targets LXRβ and GR.