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

作者：Chunge Zhong, Shengnan Wang, Wenjie Jiang, Zexu Li, Xiaofeng Wang, Shuangshuang Fan, Jun Huang, Hua‐Jun Wu, Ren Sheng, Fei Teng · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-90532-z · 被引用次数：8 · 研究领域：Cancer-related Molecular Pathways、Drug Transport and Resistance Mechanisms、DNA Repair Mechanisms

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.