Advances in clinical research of MET exon 14 skipping mutations in non-small cell lung cancer.

IF 2.7 3区 医学 Q3 ONCOLOGY
Mengchao Wang, Shao Zhang, Dan Yi, Yan Ou, Shuqi Xie, Chuanxiu Zeng, Xueqian Qin, Lu Zhao, Zhen Wang, Fanming Kong, Liwei Chen
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引用次数: 0

Abstract

The cellular-mesenchymal to epithelial transition factor (MET) gene plays a crucial role in maintaining cell homeostasis, motility, and apoptosis. In cancer, MET gene alterations promote tumour cell proliferation, invasion and metastasis. In non-small cell lung cancer (NSCLC), MET gene alterations include MET exon 14 (METex14) skipping mutation (METΔ14ex), MET amplification (METamp), MET fusion, and MET tyrosine kinase domain missense mutations (MET-TKD) and MET protein overexpression. Among them, the METΔ14ex is an independent driver gene of NSCLC. Three to four per cent of NSCLC patients carry METΔ14ex, and these patients have a poor prognosis and respond poorly to conventional chemotherapy. Small molecule highly selective MET inhibitors such as carmatinib, tepotinib, and cervotinib have shown promising efficacy and safety in clinical trials. Monoclonal antibodies, bispecific antibodies, antibody conjugate drugs, and immune checkpoint inhibitors provide more treatment space for patients with METΔ14ex. In this review, we summarize the current application and research of MET inhibitors and immune checkpoint inhibitors in NSCLC with METΔ14ex and provide recommendations for precise treatment of NSCLC patients with MET gene changes mutations. It also provides new ideas for solving the problems of synergistic effect and drug resistance in targeted therapy and immunotherapy.

非小细胞肺癌MET外显子14跳变的临床研究进展。
细胞间充质向上皮转化因子(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。在癌症中,MET基因的改变促进肿瘤细胞的增殖、侵袭和转移。在非小细胞肺癌(NSCLC)中,MET基因改变包括MET外显子14 (METex14)跳变(METΔ14ex)、MET扩增(METamp)、MET融合、MET酪氨酸激酶结构域错义突变(MET- tkd)和MET蛋白过表达。其中METΔ14ex是NSCLC的独立驱动基因。3%到4%的NSCLC患者携带METΔ14ex,这些患者预后较差,对常规化疗反应较差。小分子高选择性MET抑制剂如卡马替尼、替波替尼和cervotinib在临床试验中显示出良好的疗效和安全性。单克隆抗体、双特异性抗体、抗体偶联药物和免疫检查点抑制剂为METΔ14ex患者提供了更大的治疗空间。本文通过METΔ14ex综述MET抑制剂和免疫检查点抑制剂在NSCLC中的应用和研究现状,并为MET基因改变突变的NSCLC患者的精准治疗提供建议。这也为解决靶向治疗和免疫治疗中的协同效应和耐药问题提供了新的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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