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Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma
Glioblastoma multiforme (GBM), the most common primary brain tumor in adults, is almost never curable with the current standard treatment consisting of surgical resection, irradiation and temozolomide. The prognosis remains poor despite undisputable advances in the understanding of this tumor’s mole...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712701/ https://www.ncbi.nlm.nih.gov/pubmed/24213322 http://dx.doi.org/10.3390/cancers4020523 |
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author | Pala, Andrej Karpel-Massler, Georg Kast, Richard Eric Wirtz, Christian Rainer Halatsch, Marc-Eric |
author_facet | Pala, Andrej Karpel-Massler, Georg Kast, Richard Eric Wirtz, Christian Rainer Halatsch, Marc-Eric |
author_sort | Pala, Andrej |
collection | PubMed |
description | Glioblastoma multiforme (GBM), the most common primary brain tumor in adults, is almost never curable with the current standard treatment consisting of surgical resection, irradiation and temozolomide. The prognosis remains poor despite undisputable advances in the understanding of this tumor’s molecular biology and pathophysiology, which unfortunately has so far failed to translate into a meaningful clinical benefit. Dysregulation and a resulting prominent pathophysiological role of the epidermal growth factor receptor (EGFR) have been identified in several different malignant tumor entities, GBM among them. The EGFR is overexpressed in about 40% of GBM cases, and half of these coexpress a mutant, constitutively activated subtype, EGFRvIII. Unfortunately, recent trials studying with therapeutic approaches targeted against the EGFR and EGFRvIII have failed to meet expectations, with only a minority of patients responding despite evidence of good in vitro and rodent model activity. Having potentially high relevance within this context, epithelial to mesenchymal transition (EMT) is a phenomenon associated with early stages of carcinogenesis, cancer invasion and recurrence. During EMT, epithelial cells lose many of their epithelial characteristics, prominently E-cadherin expression, and acquire properties that are typical for mesenchymal cells such as the expression of vimentin. Epithelial to mesenchymal transition has been specifically demonstrated in GBM. In this review, we summarize the evidence that EMT may precipitate GBM resistance to EGFR-targeted therapy, and may thus be among the principal factors contributing to the clinical failure of targeted therapy against EGFR and EGFRvIII. |
format | Online Article Text |
id | pubmed-3712701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-37127012013-08-05 Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma Pala, Andrej Karpel-Massler, Georg Kast, Richard Eric Wirtz, Christian Rainer Halatsch, Marc-Eric Cancers (Basel) Review Glioblastoma multiforme (GBM), the most common primary brain tumor in adults, is almost never curable with the current standard treatment consisting of surgical resection, irradiation and temozolomide. The prognosis remains poor despite undisputable advances in the understanding of this tumor’s molecular biology and pathophysiology, which unfortunately has so far failed to translate into a meaningful clinical benefit. Dysregulation and a resulting prominent pathophysiological role of the epidermal growth factor receptor (EGFR) have been identified in several different malignant tumor entities, GBM among them. The EGFR is overexpressed in about 40% of GBM cases, and half of these coexpress a mutant, constitutively activated subtype, EGFRvIII. Unfortunately, recent trials studying with therapeutic approaches targeted against the EGFR and EGFRvIII have failed to meet expectations, with only a minority of patients responding despite evidence of good in vitro and rodent model activity. Having potentially high relevance within this context, epithelial to mesenchymal transition (EMT) is a phenomenon associated with early stages of carcinogenesis, cancer invasion and recurrence. During EMT, epithelial cells lose many of their epithelial characteristics, prominently E-cadherin expression, and acquire properties that are typical for mesenchymal cells such as the expression of vimentin. Epithelial to mesenchymal transition has been specifically demonstrated in GBM. In this review, we summarize the evidence that EMT may precipitate GBM resistance to EGFR-targeted therapy, and may thus be among the principal factors contributing to the clinical failure of targeted therapy against EGFR and EGFRvIII. MDPI 2012-05-08 /pmc/articles/PMC3712701/ /pubmed/24213322 http://dx.doi.org/10.3390/cancers4020523 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Review Pala, Andrej Karpel-Massler, Georg Kast, Richard Eric Wirtz, Christian Rainer Halatsch, Marc-Eric Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma |
title | Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma |
title_full | Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma |
title_fullStr | Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma |
title_full_unstemmed | Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma |
title_short | Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma |
title_sort | epidermal to mesenchymal transition and failure of egfr-targeted therapy in glioblastoma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712701/ https://www.ncbi.nlm.nih.gov/pubmed/24213322 http://dx.doi.org/10.3390/cancers4020523 |
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