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Napabucasin + oxaliplatin + irinotecan + fluorouracil is an investigational **combination therapy** explored primarily for **advanced or metastatic colorectal cancer** and potentially other solid tumors. Napabucasin is an orally administered **small molecule** that inhibits cancer stemness by interfering with signal transducer and activator of transcription 3 (**STAT3**)–driven gene transcription, downregulating β-catenin and PD-L1, and disrupting multiple pathways linked to cell proliferation, apoptosis, stemness, drug resistance, and metastasis[2][3][5][6]. In combination, oxaliplatin (a platinum-based DNA crosslinker), irinotecan (a topoisomerase I inhibitor), and fluorouracil (a pyrimidine analog inhibiting thymidylate synthase) constitute standard backbone chemotherapy regimens for metastatic colorectal cancer such as FOLFIRINOX or FOLFIRI[3][5]. The aim of combining napabucasin with FOLFIRI or FOLFOX (fluorouracil + oxaliplatin) regimens is to **overcome therapeutic resistance** and improve clinical outcomes by targeting both cancer stemness and tumor bulk[3][5][2].
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