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Lenvatinib + erlotinib is an investigational combination therapy consisting of two small molecule tyrosine kinase inhibitors. Lenvatinib inhibits multiple receptor tyrosine kinases involved in tumor angiogenesis and proliferation, including vascular endothelial growth factor receptors 1–3 (VEGFR1–3), fibroblast growth factor receptors 1–4 (FGFR1–4), platelet-derived growth factor receptor alpha (PDGFRα), KIT, and RET. Erlotinib selectively inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase. The rationale for combining these agents is based on evidence that EGFR activation can mediate resistance to lenvatinib in certain cancers such as hepatocellular carcinoma; thus, dual inhibition may overcome resistance mechanisms and enhance antitumor efficacy[1][5]. This combination is under clinical investigation for advanced solid tumors, including hepatocellular carcinoma[3][4][6].
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