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Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer

It has been over three decades since the hepatocyte growth factor (HGF) ligand and its receptor MET proto-oncogene (MET) pathway was established as promoting cancer growth and metastasis. MET exon 14 skipping (METex14) alterations occur in 3–4% of all non-small cell lung cancer (NSCLC) patients, typ...

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Autores principales: Hong, Lingzhi, Zhang, Jianjun, Heymach, John V., Le, Xiuning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890719/
https://www.ncbi.nlm.nih.gov/pubmed/33643443
http://dx.doi.org/10.1177/1758835921992976
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author Hong, Lingzhi
Zhang, Jianjun
Heymach, John V.
Le, Xiuning
author_facet Hong, Lingzhi
Zhang, Jianjun
Heymach, John V.
Le, Xiuning
author_sort Hong, Lingzhi
collection PubMed
description It has been over three decades since the hepatocyte growth factor (HGF) ligand and its receptor MET proto-oncogene (MET) pathway was established as promoting cancer growth and metastasis. MET exon 14 skipping (METex14) alterations occur in 3–4% of all non-small cell lung cancer (NSCLC) patients, typically in elderly patients (older than 70 years), and result in constitutive activation of the MET receptor by altering a region required for receptor degradation. Multi-kinase inhibitor of MET, such as crizotinib, and more recently selective MET inhibitors, such as capmatinib and tepotinib, have demonstrated clinical efficacy and safety in METex14 NSCLC patients in clinical trials. These results have led to the approval of MET inhibitors by regulatory agencies across the globe. The success also fueled the excitement of further development of therapeutic strategies to target METex14 in lung cancers. This article provides an overview of the clinical development program targeting METex14 in NSCLC, including small molecular tyrosine kinase inhibitors and anti-MET antibodies. Furthermore, combination therapy immune checkpoint inhibitors or other targeted therapies are also under development in various patient populations, with acquired resistance immune or targeted therapy. Clinical trials in different development stages are ongoing and more drugs targeted to c-MET will be available for NSCLC patients with METex14 skipping mutations in the future.
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spelling pubmed-78907192021-02-26 Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer Hong, Lingzhi Zhang, Jianjun Heymach, John V. Le, Xiuning Ther Adv Med Oncol Review It has been over three decades since the hepatocyte growth factor (HGF) ligand and its receptor MET proto-oncogene (MET) pathway was established as promoting cancer growth and metastasis. MET exon 14 skipping (METex14) alterations occur in 3–4% of all non-small cell lung cancer (NSCLC) patients, typically in elderly patients (older than 70 years), and result in constitutive activation of the MET receptor by altering a region required for receptor degradation. Multi-kinase inhibitor of MET, such as crizotinib, and more recently selective MET inhibitors, such as capmatinib and tepotinib, have demonstrated clinical efficacy and safety in METex14 NSCLC patients in clinical trials. These results have led to the approval of MET inhibitors by regulatory agencies across the globe. The success also fueled the excitement of further development of therapeutic strategies to target METex14 in lung cancers. This article provides an overview of the clinical development program targeting METex14 in NSCLC, including small molecular tyrosine kinase inhibitors and anti-MET antibodies. Furthermore, combination therapy immune checkpoint inhibitors or other targeted therapies are also under development in various patient populations, with acquired resistance immune or targeted therapy. Clinical trials in different development stages are ongoing and more drugs targeted to c-MET will be available for NSCLC patients with METex14 skipping mutations in the future. SAGE Publications 2021-02-15 /pmc/articles/PMC7890719/ /pubmed/33643443 http://dx.doi.org/10.1177/1758835921992976 Text en © The Author(s), 2021 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Hong, Lingzhi
Zhang, Jianjun
Heymach, John V.
Le, Xiuning
Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer
title Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer
title_full Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer
title_fullStr Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer
title_full_unstemmed Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer
title_short Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer
title_sort current and future treatment options for met exon 14 skipping alterations in non-small cell lung cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890719/
https://www.ncbi.nlm.nih.gov/pubmed/33643443
http://dx.doi.org/10.1177/1758835921992976
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