机构：[1]Mahidol Univ, Ramathibodi Hosp, Fac Med, Dept Internal Med,Div Med Oncol, Bangkok 10400, Thailand;[2]Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Dept Med Oncol,State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China;临床科室其他部门内科华南肿瘤学国家重点实验室中山大学肿瘤防治中心[3]Long Beach Vet Adm Hosp, Long Beach, CA 90822 USA;[4]Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Sch Med, Dept Med,Div Hematol Oncol, Orange County, CA 92868 USA;[5]Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Dept Med,Div Hematol Med Oncol, 101 City Dr,Bldg 56,RT 81,Rm 241, Orange County, CA 92868 USA
A number of small molecule tyrosine kinase inhibitors (TKIs) have now been approved for the treatment of non-small cell lung cancers (NSCLC), including those targeted against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. Despite a wealth of agents developed to target the receptor tyrosine kinase, MET, clinical outcomes have as yet been disappointing, leading to pessimism about the role of MET in the pathogenesis of NSCLC. However, in recent years, there has been a renewed interest in MET exon 14 alterations as potential drivers of lung cancer. MET exon 14 alterations, which result in increased MET protein levels due to disrupted ubiquitin-mediated degradation, occur at a prevalence of around 3% in adenocarcinomas and around 2% in other lung neoplasms, making them attractive targets for the treatment of lung cancer. At least five MET-targeted TKIs, including crizotinib, cabozantinib, capmatinib, tepotinib, and glesatinib, are being investigated clinically for patients with MET exon 14 altered-NSCLC. A further two compounds have shown activity in preclinical models. In this article, we review the current clinical and preclinical data available for these TKIs, along with a number of other potential therapeutic options, including antibodies and immunotherapy. A number of questions remain unanswered regarding the future of MET TKIs, but unfortunately, the development of resistance to targeted therapies is inevitable. Resistance is expected to arise as a result of receptor tyrosine kinase mutation or from upregulation of MET ligand expression; potential strategies to overcome resistance are proposed. (C) 2016 The Author(s). Published by Elsevier Ireland Ltd.
基金：
Novartis Pharmaceuticals CorporationNovartis
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区呼吸系统3 区肿瘤学
最新[2023]版：
大类|2 区医学
小类|3 区肿瘤学3 区呼吸系统
第一作者：
第一作者机构：[1]Mahidol Univ, Ramathibodi Hosp, Fac Med, Dept Internal Med,Div Med Oncol, Bangkok 10400, Thailand;
通讯作者：
通讯机构：[4]Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Sch Med, Dept Med,Div Hematol Oncol, Orange County, CA 92868 USA;[5]Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Dept Med,Div Hematol Med Oncol, 101 City Dr,Bldg 56,RT 81,Rm 241, Orange County, CA 92868 USA
推荐引用方式(GB/T 7714)：
Reungwetwattana Thanyanan,Liang Ying,Zhu Viola,et al.The race to target MET exon 14 skipping alterations in non-small cell lung cancer: The Why, the How, the Who, the Unknown, and the Inevitable[J].LUNG CANCER.2017,103:27-37.doi:10.1016/j.lungcan.2016.11.011.
APA：
Reungwetwattana, Thanyanan,Liang, Ying,Zhu, Viola&Ou, Sai-Hong Ignatius.(2017).The race to target MET exon 14 skipping alterations in non-small cell lung cancer: The Why, the How, the Who, the Unknown, and the Inevitable.LUNG CANCER,103,
MLA：
Reungwetwattana, Thanyanan,et al."The race to target MET exon 14 skipping alterations in non-small cell lung cancer: The Why, the How, the Who, the Unknown, and the Inevitable".LUNG CANCER 103.(2017):27-37
