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Crizotinib + dacomitinib is a combination of two small molecule tyrosine kinase inhibitors investigated for the treatment of advanced non-small cell lung cancer (NSCLC). Crizotinib targets and inhibits anaplastic lymphoma kinase (ALK), ROS1, and mesenchymal epithelial transition factor (MET) receptor tyrosine kinases, thereby blocking signaling pathways that promote tumor cell proliferation and survival. Dacomitinib is an irreversible inhibitor of the human epidermal growth factor receptor (EGFR/HER1), HER2, and HER4 tyrosine kinases, covalently binding to cysteine residues in their catalytic domains to block downstream signaling involved in tumor growth and resistance. The combination was studied primarily in patients with NSCLC who had progressed after prior therapies; however, clinical trials showed limited antitumor activity with substantial toxicity[1][2][3].
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