Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges

Toshio Fujino, Kenichi Suda, Tetsuya Mitsudomi Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanCorrespondence: Tetsuya MitsudomiKindai University Faculty of Medicine, Division of Thoracic Surgery, Department of Surgery, 377-2 Ohno-Higash...

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Autores principales:	Fujino T, Suda K, Mitsudomi T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	non-small cell lung cancer met exon 14 skipping capmatinib tepotinib resistance mechanisms immune checkpoint inhibitors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f984ebd2259242cf97186c7a243e1fc5
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spelling	oai:doaj.org-article:f984ebd2259242cf97186c7a243e1fc52021-12-02T15:53:36ZLung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges1179-2728https://doaj.org/article/f984ebd2259242cf97186c7a243e1fc52021-05-01T00:00:00Zhttps://www.dovepress.com/lung-cancer-with-met-exon-14-skipping-mutation-genetic-feature-current-peer-reviewed-fulltext-article-LCTThttps://doaj.org/toc/1179-2728Toshio Fujino, Kenichi Suda, Tetsuya Mitsudomi Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanCorrespondence: Tetsuya MitsudomiKindai University Faculty of Medicine, Division of Thoracic Surgery, Department of Surgery, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, JapanTel +81 72 366 0221Fax +81 72 365 7161Email mitsudom@med.kindai.ac.jpAbstract: MET exon 14 skipping mutation (MET∆ex14) is present about 3% of non-small cell lung cancers (NSCLCs). NSCLC patients with MET∆ex14 are characterized by an average age of over 70 years at diagnosis, a smoking history and a higher frequency in pleomorphic carcinoma and adenosquamous cell carcinoma than in adenocarcinoma. It has also been reported that NSCLCs with MET∆ex14 often have codriver alterations such as EGFR amplification (6– 28%), FGFR1 alterations (5– 17%), KRAS alterations (&sim; 8%), BRAF alterations (&sim; 21%), or PIK3CA mutation/amplification (&sim; 14%). In 2020, the approval of two MET-tyrosine kinase inhibitors (TKIs), capmatinib and tepotinib, for NSCLCs carrying MET∆ex14 dawned a new era for MET-targeted therapy. These drugs yielded progression-free survival of 5.4− 12.4 months in clinical trials; however, it has also been reported that one-third to half of patients show inherent resistance to MET-TKIs. In addition, the emergence of acquired resistance to MET-TKIs is inevitable. In this review, we summarize the clinical and molecular characteristics of NSCLCs with MET∆ex14, the efficacy and safety of capmatinib and tepotinib, the inherent and acquired resistance mechanisms to MET-TKIs, and new treatment strategies for NSCLCs with MET∆ex14 in the near future.Keywords: non-small cell lung cancer, MET exon 14 skipping, capmatinib, tepotinib, resistance mechanisms, immune checkpoint inhibitorsFujino TSuda KMitsudomi TDove Medical Pressarticlenon-small cell lung cancermet exon 14 skippingcapmatinibtepotinibresistance mechanismsimmune checkpoint inhibitorsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 12, Pp 35-50 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	non-small cell lung cancer met exon 14 skipping capmatinib tepotinib resistance mechanisms immune checkpoint inhibitors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	non-small cell lung cancer met exon 14 skipping capmatinib tepotinib resistance mechanisms immune checkpoint inhibitors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Fujino T Suda K Mitsudomi T Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges
description	Toshio Fujino, Kenichi Suda, Tetsuya Mitsudomi Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanCorrespondence: Tetsuya MitsudomiKindai University Faculty of Medicine, Division of Thoracic Surgery, Department of Surgery, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, JapanTel +81 72 366 0221Fax +81 72 365 7161Email mitsudom@med.kindai.ac.jpAbstract: MET exon 14 skipping mutation (MET∆ex14) is present about 3% of non-small cell lung cancers (NSCLCs). NSCLC patients with MET∆ex14 are characterized by an average age of over 70 years at diagnosis, a smoking history and a higher frequency in pleomorphic carcinoma and adenosquamous cell carcinoma than in adenocarcinoma. It has also been reported that NSCLCs with MET∆ex14 often have codriver alterations such as EGFR amplification (6– 28%), FGFR1 alterations (5– 17%), KRAS alterations (&sim; 8%), BRAF alterations (&sim; 21%), or PIK3CA mutation/amplification (&sim; 14%). In 2020, the approval of two MET-tyrosine kinase inhibitors (TKIs), capmatinib and tepotinib, for NSCLCs carrying MET∆ex14 dawned a new era for MET-targeted therapy. These drugs yielded progression-free survival of 5.4− 12.4 months in clinical trials; however, it has also been reported that one-third to half of patients show inherent resistance to MET-TKIs. In addition, the emergence of acquired resistance to MET-TKIs is inevitable. In this review, we summarize the clinical and molecular characteristics of NSCLCs with MET∆ex14, the efficacy and safety of capmatinib and tepotinib, the inherent and acquired resistance mechanisms to MET-TKIs, and new treatment strategies for NSCLCs with MET∆ex14 in the near future.Keywords: non-small cell lung cancer, MET exon 14 skipping, capmatinib, tepotinib, resistance mechanisms, immune checkpoint inhibitors
format	article
author	Fujino T Suda K Mitsudomi T
author_facet	Fujino T Suda K Mitsudomi T
author_sort	Fujino T
title	Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges
title_short	Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges
title_full	Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges
title_fullStr	Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges
title_full_unstemmed	Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges
title_sort	lung cancer with met exon 14 skipping mutation: genetic feature, current treatments, and future challenges
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/f984ebd2259242cf97186c7a243e1fc5
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Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges

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