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Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer
Hepatocyte growth factor (HGF) is the ligand for the tyrosine kinase receptor c-Met (Mesenchymal Epithelial Transition Factor also known as Hepatocyte Growth Factor Receptor, HGFR), a receptor with expression throughout epithelial and endothelial cell types. Activation of c-Met enhances cell prolife...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162713/ https://www.ncbi.nlm.nih.gov/pubmed/30134579 http://dx.doi.org/10.3390/cancers10090280 |
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author | Miranda, Oshin Farooqui, Mariya Siegfried, Jill M. |
author_facet | Miranda, Oshin Farooqui, Mariya Siegfried, Jill M. |
author_sort | Miranda, Oshin |
collection | PubMed |
description | Hepatocyte growth factor (HGF) is the ligand for the tyrosine kinase receptor c-Met (Mesenchymal Epithelial Transition Factor also known as Hepatocyte Growth Factor Receptor, HGFR), a receptor with expression throughout epithelial and endothelial cell types. Activation of c-Met enhances cell proliferation, invasion, survival, angiogenesis, and motility. The c-Met pathway also stimulates tissue repair in normal cells. A body of past research shows that increased levels of HGF and/or overexpression of c-Met are associated with poor prognosis in several solid tumors, including lung cancer, as well as cancers of the head and neck, gastro-intestinal tract, breast, ovary and cervix. The HGF/c-Met signaling network is complex; both ligand-dependent and ligand-independent signaling occur. This article will provide an update on signaling through the HGF/c-Met axis, the mechanism of action of HGF/c-Met inhibitors, the lung cancer patient populations most likely to benefit, and possible mechanisms of resistance to these inhibitors. Although c-Met as a target in non-small cell lung cancer (NSCLC) showed promise based on preclinical data, clinical responses in NSCLC patients have been disappointing in the absence of MET mutation or MET gene amplification. New therapeutics that selectively target c-Met or HGF, or that target c-Met and a wider spectrum of interacting tyrosine kinases, will be discussed. |
format | Online Article Text |
id | pubmed-6162713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61627132018-10-02 Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer Miranda, Oshin Farooqui, Mariya Siegfried, Jill M. Cancers (Basel) Review Hepatocyte growth factor (HGF) is the ligand for the tyrosine kinase receptor c-Met (Mesenchymal Epithelial Transition Factor also known as Hepatocyte Growth Factor Receptor, HGFR), a receptor with expression throughout epithelial and endothelial cell types. Activation of c-Met enhances cell proliferation, invasion, survival, angiogenesis, and motility. The c-Met pathway also stimulates tissue repair in normal cells. A body of past research shows that increased levels of HGF and/or overexpression of c-Met are associated with poor prognosis in several solid tumors, including lung cancer, as well as cancers of the head and neck, gastro-intestinal tract, breast, ovary and cervix. The HGF/c-Met signaling network is complex; both ligand-dependent and ligand-independent signaling occur. This article will provide an update on signaling through the HGF/c-Met axis, the mechanism of action of HGF/c-Met inhibitors, the lung cancer patient populations most likely to benefit, and possible mechanisms of resistance to these inhibitors. Although c-Met as a target in non-small cell lung cancer (NSCLC) showed promise based on preclinical data, clinical responses in NSCLC patients have been disappointing in the absence of MET mutation or MET gene amplification. New therapeutics that selectively target c-Met or HGF, or that target c-Met and a wider spectrum of interacting tyrosine kinases, will be discussed. MDPI 2018-08-21 /pmc/articles/PMC6162713/ /pubmed/30134579 http://dx.doi.org/10.3390/cancers10090280 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Miranda, Oshin Farooqui, Mariya Siegfried, Jill M. Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer |
title | Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer |
title_full | Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer |
title_fullStr | Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer |
title_full_unstemmed | Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer |
title_short | Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer |
title_sort | status of agents targeting the hgf/c-met axis in lung cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162713/ https://www.ncbi.nlm.nih.gov/pubmed/30134579 http://dx.doi.org/10.3390/cancers10090280 |
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