非小细胞肺癌<italic style="font-style: italic">MET</italic>基因改变及治疗进展

李俭; 陆舜

doi:10.16016/j.2097-0927.202208115

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非小细胞肺癌MET基因改变及治疗进展

专题报道：肺癌靶向治疗 | 更新时间：2026-02-13

- 非小细胞肺癌MET基因改变及治疗进展
- MET alterations and therapeutic strategies in non-small cell lung cancer
- 陆军军医大学学报 2022年44卷第24期页码：2453-2464
- 作者机构：
  
  200030 上海，上海交通大学医学院附属胸科医院
- 作者简介：
  
  [ 陆舜，博士，二级教授，主任医师，博士研究生导师。国家科技部重点专项首席专家，国务院特殊津贴获得者，上海市领军人才，上海市优秀学术带头人，上海市优秀医苑新星。目前担任上海交通大学附属胸科医院肿瘤科主任，上海市肺部肿瘤临床医学中心主任。作为第一负责人承担国家科技部重点专项、科技部国际合作课题、国家自然基金重点项目、面上项目等多项课题。2019年获"国之名医"称号，2020年获上海市劳模称号，2021年入选"国家卫生健康突出贡献中青年家"。作为第一负责人获得中国抗癌协会一等奖、上海市医学科技奖一等奖、华夏医学科技奖二等奖及上海市科技进步一等奖等。作为第一/通讯作者发表学术论文200余篇，其中SCI收录90余篇，包括《Lancet Oncol》、《Lancet Respir Med》、《J Clin Oncol》、《J Thorac Oncol》、《Nat Commun》、《Proc Natl Acad Sci U S A》、《Ann Oncol》、《ClinCancer Res》等知名杂志，总IF：338.9。目前担任美国临床肿瘤学会(ASCO)亚太区协会中国代表、多学科诊治小组(MCMC)成员，国际肺癌研究会(IASLC)出版委员会委员，国际肺癌研究会官方杂志《J Thorac Oncol》副主编，《Lung Cancer》副主编，《Oncologist》杂志编委，中华医学会肿瘤学会委员、中国抗癌协会肺癌专业委员会主任委员、中国临床肿瘤学会(CSCO)常务理事、希斯科基金会副理事长、上海市医学会理事及肿瘤学分会主任委员等职务。作为知名专家参与多项国际肺癌指南的制定。E-mail: shunlu@sjtu.edu.cn LU Shun, E-mail: shunlu@sjtu.edu.cn
- 基金信息：
  
  国家自然科学基金重点项目(82030045);上海市胸科医院肺癌中心“平台+项目”框架建设(2020NMDTP)
- DOI：10.16016/j.2097-0927.202208115
  中图分类号： R394.3;R730.53;R734.2
- 收稿：2022-08-17，
  
  修回：2022-10-28，
  
  纸质出版：2022-12-30
- 稿件说明：
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李俭, 陆舜. 非小细胞肺癌MET基因改变及治疗进展[J]. 陆军军医大学学报, 2022,44(24):2453-2464.

Jian LI, Shun LU. MET alterations and therapeutic strategies in non-small cell lung cancer[J]. Journal of Army Medical University, 2022, 44(24): 2453-2464.
李俭, 陆舜. 非小细胞肺癌MET基因改变及治疗进展[J]. 陆军军医大学学报, 2022,44(24):2453-2464. DOI： 10.16016/j.2097-0927.202208115.

Jian LI, Shun LU. MET alterations and therapeutic strategies in non-small cell lung cancer[J]. Journal of Army Medical University, 2022, 44(24): 2453-2464. DOI： 10.16016/j.2097-0927.202208115.

摘要

MET

基因在维持细胞稳态、运动和凋亡中起着至关重要的作用。在肿瘤中，

MET

基因改变促进肿瘤细胞的增殖、侵袭和转移。在非小细胞肺癌(non-small cell lung cancer，NSCLC)中，

MET

基因改变包括

MET

14号外显子跳跃突变(

MET

ex14)、

MET

扩增(

MET

amp)、

MET

融合(

MET

fusion)、MET酪氨酸激酶区域的错义突变(MET-tyrosine kinase domain，MET-TKD)和MET蛋白过度表达。基于对

MET

基因及信号通路的认识，研究者们提出了三种靶向

MET

的方法：

MET

酪氨酸激酶抑制剂(tyrosine kinase inhibitor，TKI)，包括克唑替尼、卡马替尼、特泊替尼、赛沃替尼和卡博替尼；

MET

或其配体肝细胞生长因子(hepatocyte growth factor，HGF)单克隆抗体，包括依玛妥珠单抗(Emibetuzumab)，AV-299(Ficlatuzumab)；和MET或HGF抗体偶联药物和双特异性抗体，包括替利妥珠单抗(Telisotuzumab vedotin)和埃万妥单抗(Amivantamab)。本文对

MET

基因改变及其治疗进展进行述评，以期为

MET

基因改变的NSCLC患者的精准治疗推荐意见，为解决靶向治疗和免疫治疗的增效和耐药问题提供新思路。

Abstract

Mesenchymal to epithelial transition factor (

MET

) often plays a crucial role in cell homeostasis

motility and apoptosis

while its alterations can promote the proliferation

invasion and metastasis of tumors cells. In non-small cell lung cancer (NSCLC)

MET

genetic alterations include

MET

exon 14 skipping mutations

MET

amplification

MET

fusion

MET-tyrosine kinase domain and overexpression. Based on the understanding of the potential therapeutic targets of

MET

the investigators propose 3 strategies of MET targeting for clinical t

rials: MET tyrosine kinase inhibitors (TKIs)

including crizotinib

capmatinib

tepotinib

savolitinib

and cabozantinib; MET or hepatocyte growth factor (HGF) monoclonal antibodies

including emibetuzumab vedotin and ficlatuzumab; and MET or HGF antibody-drug conjugate and bispecific antibodies

including telisotuzumab and amivantamab. In this article

we review the progress of MET genetic alteration and its treatment progress

hope to provide more precise treatment for the patients with MET alterations

and provide new ideas for the efficacy and drug resistance of targeted therapy and immunotherapy.

关键词

Keywords

references

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DOI：10.16016/j.2097-0927.202208115

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