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Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer
METex14 skipping mutations occur in about 3–4% of lung adenocarcinoma patients and 1–2% of patients with other lung cancer histology. The MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are established oncogenic drivers of NSCLC. A mutation that results in loss of exon 14...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381548/ https://www.ncbi.nlm.nih.gov/pubmed/34425853 http://dx.doi.org/10.1186/s13045-021-01138-7 |
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author | Drusbosky, Leylah M. Dawar, Richa Rodriguez, Estelamari Ikpeazu, Chukwuemeka V. |
author_facet | Drusbosky, Leylah M. Dawar, Richa Rodriguez, Estelamari Ikpeazu, Chukwuemeka V. |
author_sort | Drusbosky, Leylah M. |
collection | PubMed |
description | METex14 skipping mutations occur in about 3–4% of lung adenocarcinoma patients and 1–2% of patients with other lung cancer histology. The MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are established oncogenic drivers of NSCLC. A mutation that results in loss of exon 14 in the MET gene leads to dysregulation and inappropriate signaling that is associated with increased responsiveness to MET TKIs. Results from GEOMETRY mono-1 and VISION Phase I/II clinical trials demonstrated significant clinical activity in patients treated with the MET Exon 14 skipping mutation inhibitors capmatinib and tepotinib with tolerable toxicity profile. In the GEOMETRY mono-1 trial, capmatinib was especially active in treatment-naïve patients supporting the upfront testing of this oncogenic driver. Tepotinib demonstrated superior activity in the pretreated patients in the VISION trial. Savolitinib is another MET TKI that has shown efficacy in the first- and second-line settings, including patients with aggressive pulmonary sarcomatoid carcinoma. These studies have demonstrated that these TKIs can cross the blood brain barrier and demonstrated some activity toward CNS metastases. MET Exon 14 skipping mutation is detected by NGS-based testing of liquid or tissue biopsies, with preference for RNA-based NGS. The activity of capmatinib and tepotinib is limited by the development of acquired resistance. Current research is focused on strategies to overcome resistance and improve the effectiveness of these agents. Our aim is to review the current status of MET Exon 14 skipping mutation as it pertains NSCLC. |
format | Online Article Text |
id | pubmed-8381548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83815482021-08-23 Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer Drusbosky, Leylah M. Dawar, Richa Rodriguez, Estelamari Ikpeazu, Chukwuemeka V. J Hematol Oncol Review METex14 skipping mutations occur in about 3–4% of lung adenocarcinoma patients and 1–2% of patients with other lung cancer histology. The MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are established oncogenic drivers of NSCLC. A mutation that results in loss of exon 14 in the MET gene leads to dysregulation and inappropriate signaling that is associated with increased responsiveness to MET TKIs. Results from GEOMETRY mono-1 and VISION Phase I/II clinical trials demonstrated significant clinical activity in patients treated with the MET Exon 14 skipping mutation inhibitors capmatinib and tepotinib with tolerable toxicity profile. In the GEOMETRY mono-1 trial, capmatinib was especially active in treatment-naïve patients supporting the upfront testing of this oncogenic driver. Tepotinib demonstrated superior activity in the pretreated patients in the VISION trial. Savolitinib is another MET TKI that has shown efficacy in the first- and second-line settings, including patients with aggressive pulmonary sarcomatoid carcinoma. These studies have demonstrated that these TKIs can cross the blood brain barrier and demonstrated some activity toward CNS metastases. MET Exon 14 skipping mutation is detected by NGS-based testing of liquid or tissue biopsies, with preference for RNA-based NGS. The activity of capmatinib and tepotinib is limited by the development of acquired resistance. Current research is focused on strategies to overcome resistance and improve the effectiveness of these agents. Our aim is to review the current status of MET Exon 14 skipping mutation as it pertains NSCLC. BioMed Central 2021-08-23 /pmc/articles/PMC8381548/ /pubmed/34425853 http://dx.doi.org/10.1186/s13045-021-01138-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Drusbosky, Leylah M. Dawar, Richa Rodriguez, Estelamari Ikpeazu, Chukwuemeka V. Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer |
title | Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer |
title_full | Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer |
title_fullStr | Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer |
title_full_unstemmed | Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer |
title_short | Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer |
title_sort | therapeutic strategies in metex14 skipping mutated non-small cell lung cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381548/ https://www.ncbi.nlm.nih.gov/pubmed/34425853 http://dx.doi.org/10.1186/s13045-021-01138-7 |
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