biostudies-literatureWu WYNational Natural Science Foundation of China (National Science Foundation of China)703-714https://www.ebi.ac.uk/biostudies/studies/S-EPMC12867762biostudies-literatureUnknown45(6)Capecitabine has been commonly used for the treatment of early-stage triple-negative breast cancer (TNBC) patients; however, the resistance limits its curative potential. Here, we perform multi-omics data analysis and immunohistochemical (IHC) staining of biological samples from patients in the CBCSG010 clinical trial who were randomized to receive adjuvant docetaxel-anthracycline-based chemotherapy with or without capecitabine. We find that patients with a better prognosis in the capecitabine group exhibited an immune-inflamed microenvironment and upregulation of interferon pathways. Moreover, we identify interferon-related TANK-binding kinase 1-binding protein 1 (TBKBP1) as the key gene involved in capecitabine resistance. We uncover that TBKBP1 promotes capecitabine resistance through iOncogeneTBKBP1 induces capecitabine resistance through negative regulation of type I interferon pathway in triple-negative breast cancer.PMC1286776282172576Di GHYang YSShao ZMXie YFAndriani LWu WYLi JJfalseTBKBP1 induces capecitabine resistance through negative regulation of type I interferon pathway in triple-negative breast cancer.Capecitabine has been commonly used for the treatment of early-stage triple-negative breast cancer (TNBC) patients; however, the resistance limits its curative potential. Here, we perform multi-omics data analysis and immunohistochemical (IHC) staining of biological samples from patients in the CBCSG010 clinical trial who were randomized to receive adjuvant docetaxel-anthracycline-based chemotherapy with or without capecitabine. We find that patients with a better prognosis in the capecitabine group exhibited an immune-inflamed microenvironment and upregulation of interferon pathways. Moreover, we identify interferon-related TANK-binding kinase 1-binding protein 1 (TBKBP1) as the key gene involved in capecitabine resistance. We uncover that TBKBP1 promotes capecitabine resistance through i2026-01-01T00:00:00Z2026 Feb2026-07-15T06:18:15.429Z2026-06-30T03:22:50.608ZS-EPMC128677624160629410.1038/s41388-025-03598-4