Communications Biology (Oct 2022)

Rewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRAS G12D glycolytic colorectal tumors

  • Marlies C. Ludikhuize,
  • Sira Gevers,
  • Nguyen T. B. Nguyen,
  • Maaike Meerlo,
  • S. Khadijeh Shafiei Roudbari,
  • M. Can Gulersonmez,
  • Edwin C. A. Stigter,
  • Jarno Drost,
  • Hans Clevers,
  • Boudewijn M. T. Burgering,
  • Maria J. Rodríguez Colman

DOI
https://doi.org/10.1038/s42003-022-04055-8
Journal volume & issue
Vol. 5, no. 1
pp. 1 – 16

Abstract

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In p53-deficient colorectal cancer organoids, 5-fluorouracil induces pyrimidine imbalance, which causes DNA damage and cell death. Rewiring glucose metabolism through PDK inhibition by DCA enhances 5-FU toxicity in glycolytic p53-deficient organoids.