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Crizotinib is a small molecule tyrosine kinase inhibitor primarily targeting anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor (HGFR, c-MET), ROS1, and Recepteur d'Origine Nantais (RON). It is used for the treatment of ALK- or ROS1-positive non-small cell lung cancer (NSCLC), ALK-positive anaplastic large cell lymphoma (ALCL), and inflammatory myofibroblastic tumor (IMT). Crizotinib inhibits these kinases by competitively binding to their ATP-binding sites, leading to reduced phosphorylation activity, G1-S phase cell cycle arrest, and induction of apoptosis in tumor cells with relevant mutations or fusions. VEGF inhibitors are a class of drugs that block vascular endothelial growth factor signaling pathways—primarily through inhibition of VEGF receptors such as VEGFR2—thereby suppressing angiogenesis in tumors. The combination of crizotinib with a VEGF inhibitor represents a therapeutic strategy aimed at simultaneously inhibiting oncogenic signaling and tumor angiogenesis for enhanced anti-tumor efficacy[1][2][5][6].
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