The c-ros oncogene 1(ROS1)gene is primarily fused with CD74 and SLC34A in non-small cell lung cancer(NSCLC),and also fused with SDC4,EZR,TPM3,TFG,ZCCHC8,SLMAP,and MYO5C genes.The ROS1 fusion genes retain the tyrosine kinase structural domain of ROS1.When abnormally activated,the ROS1 fusion genes can activate the ROS1 tyro-sine kinase domain and downstream signaling pathways,leading to tumor growth,proliferation,migration,and invasion.Patients with ROS1 fusion-positive NSCLC are characterized by a young age of onset and a likelihood of brain metastasis.The first drug approved in China for ROS1 fusion-positive NSCLC is crizotinib,a ROS1 tyrosine kinase inhibitor.However,crizotinib is prone to developing resistance.Understanding its resistance mechanisms and how to treat ROS1-positive NSCLC after resistance has become an urgent issue that must be addressed.Highly effective and safe multi-targeted drugs bring hope to patients with ROS1-positive NSCLC.This article reviews the multi-targeted drugs for ROS1 gene-positive NSCLC and their resistance mecha-nisms.
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