多靶点药物治疗c-ros原癌基因1酪氨酸激酶阳性非小细胞肺癌研究进展  

Research progress on multi-targeted drug therapy for c-ros oncogene 1 receptor tyrosine kinase gene-positive non-small cell lung cancer

作　　者：李亚辉 李婷 穆林[3] LI Yahui;LI Ting;MU Lin(Graduate Department of Changzhi Medical College,Changzhi 046000,Shanxi Province,China;Department of Mental Health,Changzhi Medical College,Changzhi 046000,Shanxi Province,China;Department of Respiratory and Critical Care Medicine,Heping Hospital Affiliated to Changzhi Medical College,Changzhi 046000,Shanxi Province,China)

机构地区：[1]长治医学院研究生处,山西长治046000 [2]长治医学院精神卫生系,山西长治046000 [3]长治医学院附属和平医院呼吸与危重症医学科,山西长治046000

出　　处：《新乡医学院学报》2024年第7期695-700,共6页Journal of Xinxiang Medical University

摘　　要：c-ros原癌基因1酪氨酸激酶(ROS1)基因在非小细胞肺癌(NSCLC)中主要与CD74、SLC34A发生融合,其次与SDC4、EZR、TPM3、TFG、ZCCHC8、SLMAP和MYO5C等融合,ROS1融合基因均保留了ROS1的酪氨酸激酶结构域,异常活化时可以激活ROS1酪氨酸激酶区及下游信号通路,导致肿瘤的生长、增殖、迁移和侵袭。ROS1融合阳性NSCLC患者具有发病年龄小、可发生脑转移的特点,我国首次获批用于ROS1融合阳性NSCLC的药物有ROS1酪氨酸激酶抑制剂克唑替尼,但克唑替尼易发生耐药,克唑替尼的耐药机制以及耐药后的ROS1阳性NSCLC如何治疗成为亟需解决的问题,高效、安全的多靶点药物给ROS1阳性NSCLC患者带来曙光。本文就ROS1基因阳性NSCLC的多靶点药物及其耐药机制进行综述。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 tyrosine 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 mechanisms.

关 键 词：非小细胞肺癌 c-ros原癌基因1酪氨酸激酶 多靶点药物 获得性耐药 新型药物 

分 类 号：R734.2[医药卫生—肿瘤]