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A view on EGFR-targeted therapies from the oncogene-addiction perspective

Tumor cell growth and survival can often be impaired by inactivating a single oncogen– a phenomenon that has been called as “oncogene addiction.” It is in such scenarios that molecular targeted therapies may succeed. among known oncogenes, the epidermal growth factor receptor (EGFR) has become the t...

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Autores principales: Perez, Rolando, Crombet, Tania, de Leon, Joel, Moreno, Ernesto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636470/
https://www.ncbi.nlm.nih.gov/pubmed/23637683
http://dx.doi.org/10.3389/fphar.2013.00053
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author Perez, Rolando
Crombet, Tania
de Leon, Joel
Moreno, Ernesto
author_facet Perez, Rolando
Crombet, Tania
de Leon, Joel
Moreno, Ernesto
author_sort Perez, Rolando
collection PubMed
description Tumor cell growth and survival can often be impaired by inactivating a single oncogen– a phenomenon that has been called as “oncogene addiction.” It is in such scenarios that molecular targeted therapies may succeed. among known oncogenes, the epidermal growth factor receptor (EGFR) has become the target of different cancer therapies. So far, however, the clinical benefit from EGFR-targeted therapies has been rather limited. a critical review of the large amount of clinical data obtained with anti-EGFR agents, carried out from the perspective of the oncogene addiction concept, may help to understand the causes of the unsatisfactory results. In this article we intend to do such an exercise taking as basis for the analysis a few case studies of anti-EGFR agents that are currently in the clinic. There, the “EGFR addiction” phenomenon becomes apparent in high-responder patients. We further discuss how the concept of oncogene addiction needs to be interpreted on the light of emerging experimental evidences and ideas; in particular, that EGFR addiction may reflect the interconnection of several cellular pathways. In this regard we set forth several hypotheses; namely, that requirement of higher glucose uptake by hypoxic tumor cells may reinforce EGFR addiction; and that chronic use of EGFR-targeted antibodies in EGFR-addicted tumors would induce stable disease by reversing the malignant phenotype of cancer stem cells and also by sustaining an anti-tumor T cell response. Finally, we discuss possible reasons for the failure of certain combinatorial therapies involving anti-EGFR agents, arguing that some of these agents might produce either a negative or a positive trans-modulation effect on other oncogenes. It becomes evident that we need operational definitions of EGFR addiction in order to determine which patient populations may benefit from treatment with anti-EGFR drugs, and to improve the design of these therapies.
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spelling pubmed-36364702013-05-01 A view on EGFR-targeted therapies from the oncogene-addiction perspective Perez, Rolando Crombet, Tania de Leon, Joel Moreno, Ernesto Front Pharmacol Pharmacology Tumor cell growth and survival can often be impaired by inactivating a single oncogen– a phenomenon that has been called as “oncogene addiction.” It is in such scenarios that molecular targeted therapies may succeed. among known oncogenes, the epidermal growth factor receptor (EGFR) has become the target of different cancer therapies. So far, however, the clinical benefit from EGFR-targeted therapies has been rather limited. a critical review of the large amount of clinical data obtained with anti-EGFR agents, carried out from the perspective of the oncogene addiction concept, may help to understand the causes of the unsatisfactory results. In this article we intend to do such an exercise taking as basis for the analysis a few case studies of anti-EGFR agents that are currently in the clinic. There, the “EGFR addiction” phenomenon becomes apparent in high-responder patients. We further discuss how the concept of oncogene addiction needs to be interpreted on the light of emerging experimental evidences and ideas; in particular, that EGFR addiction may reflect the interconnection of several cellular pathways. In this regard we set forth several hypotheses; namely, that requirement of higher glucose uptake by hypoxic tumor cells may reinforce EGFR addiction; and that chronic use of EGFR-targeted antibodies in EGFR-addicted tumors would induce stable disease by reversing the malignant phenotype of cancer stem cells and also by sustaining an anti-tumor T cell response. Finally, we discuss possible reasons for the failure of certain combinatorial therapies involving anti-EGFR agents, arguing that some of these agents might produce either a negative or a positive trans-modulation effect on other oncogenes. It becomes evident that we need operational definitions of EGFR addiction in order to determine which patient populations may benefit from treatment with anti-EGFR drugs, and to improve the design of these therapies. Frontiers Media S.A. 2013-04-26 /pmc/articles/PMC3636470/ /pubmed/23637683 http://dx.doi.org/10.3389/fphar.2013.00053 Text en Copyright © Perez, Crombet, de Leon and Moreno. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Pharmacology
Perez, Rolando
Crombet, Tania
de Leon, Joel
Moreno, Ernesto
A view on EGFR-targeted therapies from the oncogene-addiction perspective
title A view on EGFR-targeted therapies from the oncogene-addiction perspective
title_full A view on EGFR-targeted therapies from the oncogene-addiction perspective
title_fullStr A view on EGFR-targeted therapies from the oncogene-addiction perspective
title_full_unstemmed A view on EGFR-targeted therapies from the oncogene-addiction perspective
title_short A view on EGFR-targeted therapies from the oncogene-addiction perspective
title_sort view on egfr-targeted therapies from the oncogene-addiction perspective
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636470/
https://www.ncbi.nlm.nih.gov/pubmed/23637683
http://dx.doi.org/10.3389/fphar.2013.00053
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