Scientific Reports (Feb 2025)

Chemoresistance mechanisms to 5-Fluorouracil and reversal strategies in lung and breast cancer

  • Chunge Zhong,
  • Shengnan Wang,
  • Wen-Jie Jiang,
  • Zexu Li,
  • Xiaofeng Wang,
  • Shuangshuang Fan,
  • Jun Huang,
  • Hua-Jun Wu,
  • Ren Sheng,
  • Teng Fei

DOI
https://doi.org/10.1038/s41598-025-90532-z
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 10

Abstract

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Abstract Chemotherapy drug 5-Fluorouracil (5-FU) is a major treatment for many cancers; however, its efficacy is limited by chemoresistance. Here, we investigate the resistance mechanisms to 5-FU and reversal strategies in lung and breast cancer cells. Using multiple 5-FU-resistant lung cancer and breast cancer cell models, we reveal differential cellular and molecular features of 5-FU resistance between different cancer types. We further unravel the implications of immune-related processes, NOTCH and WNT signaling with 5-FU resistance. In lung cancer, the activation of WNT/β-catenin signaling promotes the resistance and blocking this signaling re-sensitizes resistant cells to 5-FU treatment. Our study not only reveals differential features and mechanisms underlying 5-FU resistance across different cancers, but also suggests potential strategies against such resistance.

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