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**Cixutumumab + sorafenib** is a combination therapy investigated for advanced hepatocellular carcinoma (HCC). **Cixutumumab** is a recombinant human IgG1 monoclonal antibody targeting insulin-like growth factor-1 receptor (IGF-1R), inhibiting its activation by IGF-1 and IGF-II, inducing internalization and degradation of the receptor, and thereby blocking growth-promoting signaling[1][5]. **Sorafenib** is an oral small molecule multikinase inhibitor that targets the RAF/MEK/ERK pathway (blocking tumor cell proliferation) and inhibits angiogenesis via vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptor (PDGFR-β), c-Kit, FLT3, and RET[4]. The combination was evaluated to target both the IGF and VEGF pathways simultaneously, with the goal to enhance antitumor activity and overcome resistance seen in monotherapy. The combination showed manageable toxicity but limited clinical efficacy in phase I trials. The median progression-free survival for the combination was about 6 months and overall survival about 10–13 months in phase I/II trials, comparable to sorafenib alone[1][2][3][5].
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