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Mechanisms of resistance to EGFR-targeted drugs: lung cancer
Despite the improvement in clinical outcomes derived by the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumours harbour EGFR-activating mutations, prognosis remains...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070275/ https://www.ncbi.nlm.nih.gov/pubmed/27843613 http://dx.doi.org/10.1136/esmoopen-2016-000060 |
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author | Morgillo, Floriana Della Corte, Carminia Maria Fasano, Morena Ciardiello, Fortunato |
author_facet | Morgillo, Floriana Della Corte, Carminia Maria Fasano, Morena Ciardiello, Fortunato |
author_sort | Morgillo, Floriana |
collection | PubMed |
description | Despite the improvement in clinical outcomes derived by the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumours harbour EGFR-activating mutations, prognosis remains unfavourable because of the occurrence of either intrinsic or acquired resistance. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing EGFR-TKIs resistance mechanisms discovered in preclinical models and in patients with NSCLC. The molecular heterogeneity of lung cancer has several implications in terms of possible mechanisms of either intrinsic or acquired resistance to EGFR-targeted inhibitors. Several mechanisms of resistance have been described to EGFR-TKIs, such as the occurrence of secondary mutation (T790M, C797S), the activation of alternative signalling (Met, HGF, AXL, Hh, IGF-1R), the aberrance of the downstream pathways (AKT mutations, loss of PTEN), the impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism) and histological transformation. Although some of the mechanisms of resistance have been identified, much additional information is needed to understand and overcome resistance to EGFR-TKI agents. The majority of resistance mechanisms described are the result of a selection of pre-existing clones; thus, studies on the mechanisms by which subclonal alterations have an impact on tumour biology and influence cancer progression are extremely important in order to define the best treatment strategy. |
format | Online Article Text |
id | pubmed-5070275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50702752016-11-14 Mechanisms of resistance to EGFR-targeted drugs: lung cancer Morgillo, Floriana Della Corte, Carminia Maria Fasano, Morena Ciardiello, Fortunato ESMO Open Review Despite the improvement in clinical outcomes derived by the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumours harbour EGFR-activating mutations, prognosis remains unfavourable because of the occurrence of either intrinsic or acquired resistance. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing EGFR-TKIs resistance mechanisms discovered in preclinical models and in patients with NSCLC. The molecular heterogeneity of lung cancer has several implications in terms of possible mechanisms of either intrinsic or acquired resistance to EGFR-targeted inhibitors. Several mechanisms of resistance have been described to EGFR-TKIs, such as the occurrence of secondary mutation (T790M, C797S), the activation of alternative signalling (Met, HGF, AXL, Hh, IGF-1R), the aberrance of the downstream pathways (AKT mutations, loss of PTEN), the impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism) and histological transformation. Although some of the mechanisms of resistance have been identified, much additional information is needed to understand and overcome resistance to EGFR-TKI agents. The majority of resistance mechanisms described are the result of a selection of pre-existing clones; thus, studies on the mechanisms by which subclonal alterations have an impact on tumour biology and influence cancer progression are extremely important in order to define the best treatment strategy. BMJ Publishing Group 2016-05-11 /pmc/articles/PMC5070275/ /pubmed/27843613 http://dx.doi.org/10.1136/esmoopen-2016-000060 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Review Morgillo, Floriana Della Corte, Carminia Maria Fasano, Morena Ciardiello, Fortunato Mechanisms of resistance to EGFR-targeted drugs: lung cancer |
title | Mechanisms of resistance to EGFR-targeted drugs: lung cancer |
title_full | Mechanisms of resistance to EGFR-targeted drugs: lung cancer |
title_fullStr | Mechanisms of resistance to EGFR-targeted drugs: lung cancer |
title_full_unstemmed | Mechanisms of resistance to EGFR-targeted drugs: lung cancer |
title_short | Mechanisms of resistance to EGFR-targeted drugs: lung cancer |
title_sort | mechanisms of resistance to egfr-targeted drugs: lung cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070275/ https://www.ncbi.nlm.nih.gov/pubmed/27843613 http://dx.doi.org/10.1136/esmoopen-2016-000060 |
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