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Journal of Cancer Research and Clinical Oncology

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Open Access 01-02-2025 | NSCLC | Review

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

Authors: Mengchao Wang, Shao Zhang, Dan Yi, Yan Ou, Shuqi Xie, Chuanxiu Zeng, Xueqian Qin, Lu Zhao, Zhen Wang, Fanming Kong, Liwei Chen

Published in: Journal of Cancer Research and Clinical Oncology | Issue 2/2025

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.

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Title: Advances in clinical research of MET exon 14 skipping mutations in non-small cell lung cancer
Authors: Mengchao Wang
Shao Zhang
Dan Yi
Yan Ou
Shuqi Xie
Chuanxiu Zeng
Xueqian Qin
Lu Zhao
Zhen Wang
Fanming Kong
Liwei Chen
Publication date: 01-02-2025
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Targeted Therapy
Checkpoint Inhibitors
Published in: Journal of Cancer Research and Clinical Oncology / Issue 2/2025
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-025-06115-y

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