Signaling Pathways Involved in 5-FU Drug Resistance in Cancer

Cancer Invest. 2022 Jul;40(6):516-543. doi: 10.1080/07357907.2022.2055050. Epub 2022 Mar 28.

Abstract

Anti-metabolite drugs prevent the synthesis of essential cell growth compounds. 5-fluorouracil is used as an anti-metabolic drug in various cancers in the first stage of treatment. Unfortunately, in some cancers, 5-fluorouracil has low effectiveness because of its drug resistance. Studies have shown that drug resistance to 5-fluorouracil is due to the activation of specific signaling pathways and increased expressions of enzymes involved in drug metabolites. However, when 5-fluorouracil is used in combination with other drugs, the sensitivity of cancer cells to 5-fluorouracil increases, and the effect of drug resistance is reversed. This study discusses how the function of 5-fluorouracil in JAK/STAT, Wnt, Notch, NF-κB, and hedgehogs in some cancers.

Keywords: 5-fluorouracil; Hedgehog pathway; JAK/STAT pathway; NF-κB pathway; Notch pathway; Wnt pathway.

MeSH terms

  • Apoptosis*
  • Cell Line, Tumor
  • Drug Resistance
  • Drug Resistance, Neoplasm
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • NF-kappa B / metabolism
  • Neoplasms* / drug therapy
  • Signal Transduction

Substances

  • NF-kappa B
  • Fluorouracil