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MET Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential?
Gastric cancer remains a disease with a dismal prognosis. Extensive efforts to find targetable disease drivers in gastric cancer were implemented to improve patient outcomes. Beyond anti-HER2 therapy, MET pathway seems to be culprit of cancer invasiveness with MET-overexpressing tumors having poorer...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547764/ https://www.ncbi.nlm.nih.gov/pubmed/33116950 http://dx.doi.org/10.2147/JEP.S242958 |
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author | El Darsa, Haidar El Sayed, Rola Abdel-Rahman, Omar |
author_facet | El Darsa, Haidar El Sayed, Rola Abdel-Rahman, Omar |
author_sort | El Darsa, Haidar |
collection | PubMed |
description | Gastric cancer remains a disease with a dismal prognosis. Extensive efforts to find targetable disease drivers in gastric cancer were implemented to improve patient outcomes. Beyond anti-HER2 therapy, MET pathway seems to be culprit of cancer invasiveness with MET-overexpressing tumors having poorer prognosis. Tyrosine kinase inhibitors targeting the HGF/MET pathway were studied in MET-positive gastric cancer, but no substantial benefit was proven. Some patients responded in early phase trials but later developed resistance. Others failed to show any benefit at all. Etiologies of resistance may entail inappropriate patient selection with a lack of MET detection standardization, tumor alternative pathways, variable MET amplification, and genetic variation. Optimizing MET detection techniques and better understanding the MET pathway, as well as tumor bypass mechanisms, are an absolute need to devise means to overcome resistance using targeted therapy alone, or in combination with other synergistic agents to improve outcomes of patients with MET-positive GC. |
format | Online Article Text |
id | pubmed-7547764 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-75477642020-10-27 MET Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential? El Darsa, Haidar El Sayed, Rola Abdel-Rahman, Omar J Exp Pharmacol Review Gastric cancer remains a disease with a dismal prognosis. Extensive efforts to find targetable disease drivers in gastric cancer were implemented to improve patient outcomes. Beyond anti-HER2 therapy, MET pathway seems to be culprit of cancer invasiveness with MET-overexpressing tumors having poorer prognosis. Tyrosine kinase inhibitors targeting the HGF/MET pathway were studied in MET-positive gastric cancer, but no substantial benefit was proven. Some patients responded in early phase trials but later developed resistance. Others failed to show any benefit at all. Etiologies of resistance may entail inappropriate patient selection with a lack of MET detection standardization, tumor alternative pathways, variable MET amplification, and genetic variation. Optimizing MET detection techniques and better understanding the MET pathway, as well as tumor bypass mechanisms, are an absolute need to devise means to overcome resistance using targeted therapy alone, or in combination with other synergistic agents to improve outcomes of patients with MET-positive GC. Dove 2020-10-06 /pmc/articles/PMC7547764/ /pubmed/33116950 http://dx.doi.org/10.2147/JEP.S242958 Text en © 2020 El Darsa et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Review El Darsa, Haidar El Sayed, Rola Abdel-Rahman, Omar MET Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential? |
title | MET Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential? |
title_full | MET Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential? |
title_fullStr | MET Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential? |
title_full_unstemmed | MET Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential? |
title_short | MET Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential? |
title_sort | met inhibitors for the treatment of gastric cancer: what’s their potential? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547764/ https://www.ncbi.nlm.nih.gov/pubmed/33116950 http://dx.doi.org/10.2147/JEP.S242958 |
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