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These findings shed light on mechanisms underlying 5FU resistance and propose a rational strategy for combination therapy in CRC, emphasizing the potential clinical benefit of targeting mitochondrial metabolism to overcome resistance and enhance patient outcomes

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FUNDING This work was supported by the National Natural Science Foundation of China (82300903), the Key R&D Plan Social Development Project of Jiangsu Province (SBE2023741128), the National Natural Science Foundationof Jiangsu Province (SBK20 23022865), the sixth phase 333 second level talent training project of Jiangsu Province (tackling bottleneck technology) (BRA2022008), the Projects from Social Development of Zhenjiang (SH2023029), the Youth Science and Technology Talent Recruitment Project of Zhenjiang city (ZJTJ2101), the Affiliated Hospital of Jiangsu University Beigu Talent Cultivation Plan Project (BGYCB202206), the Affiliated Hospital of Jiangsu University Doctoral Initiation Fund Project (jdfykc2021005)

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