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Antiangiogeneic Strategies in Mesothelioma

There is a strong rationale for inhibiting angiogenesis in mesothelioma. Vascular endothelial growth factor (VEGF) is an autocrine growth factor in mesothelioma and a potent mitogen for mesothelial cells. Further, the abnormal tumor vasculature promotes raised interstitial pressure and hypoxia, whic...

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Autores principales: Nowak, Anna K., Brosseau, Solenn, Cook, Alistair, Zalcman, Gérard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040194/
https://www.ncbi.nlm.nih.gov/pubmed/32133285
http://dx.doi.org/10.3389/fonc.2020.00126
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author Nowak, Anna K.
Brosseau, Solenn
Cook, Alistair
Zalcman, Gérard
author_facet Nowak, Anna K.
Brosseau, Solenn
Cook, Alistair
Zalcman, Gérard
author_sort Nowak, Anna K.
collection PubMed
description There is a strong rationale for inhibiting angiogenesis in mesothelioma. Vascular endothelial growth factor (VEGF) is an autocrine growth factor in mesothelioma and a potent mitogen for mesothelial cells. Further, the abnormal tumor vasculature promotes raised interstitial pressure and hypoxia, which may be detrimental to both penetration and efficacy of anticancer agents. Antiangiogenic agents have been trialed in mesothelioma for close to two decades, with early phase clinical trials testing vascular targeting agents, the VEGF-A targeting monoclonal antibody bevacizumab, and numerous tyrosine kinase inhibitors, many with multiple targets. None of these have shown efficacy which has warranted further development as single agents in any line of therapy. Whilst a randomized phase II trial combining the multitargeted tyrosine kinase inhibitor nintedanib with platinum/pemetrexed chemotherapy was positive, these results were not confirmed in a subsequent phase III study. The combination of cisplatin and pemetrexed with bevacizumab, in appropriately selected patients, remains the only anti-angiogenic combination showing efficacy in mesothelioma. Extensive efforts to identify biomarkers of response have not yet been successful.
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spelling pubmed-70401942020-03-04 Antiangiogeneic Strategies in Mesothelioma Nowak, Anna K. Brosseau, Solenn Cook, Alistair Zalcman, Gérard Front Oncol Oncology There is a strong rationale for inhibiting angiogenesis in mesothelioma. Vascular endothelial growth factor (VEGF) is an autocrine growth factor in mesothelioma and a potent mitogen for mesothelial cells. Further, the abnormal tumor vasculature promotes raised interstitial pressure and hypoxia, which may be detrimental to both penetration and efficacy of anticancer agents. Antiangiogenic agents have been trialed in mesothelioma for close to two decades, with early phase clinical trials testing vascular targeting agents, the VEGF-A targeting monoclonal antibody bevacizumab, and numerous tyrosine kinase inhibitors, many with multiple targets. None of these have shown efficacy which has warranted further development as single agents in any line of therapy. Whilst a randomized phase II trial combining the multitargeted tyrosine kinase inhibitor nintedanib with platinum/pemetrexed chemotherapy was positive, these results were not confirmed in a subsequent phase III study. The combination of cisplatin and pemetrexed with bevacizumab, in appropriately selected patients, remains the only anti-angiogenic combination showing efficacy in mesothelioma. Extensive efforts to identify biomarkers of response have not yet been successful. Frontiers Media S.A. 2020-02-18 /pmc/articles/PMC7040194/ /pubmed/32133285 http://dx.doi.org/10.3389/fonc.2020.00126 Text en Copyright © 2020 Nowak, Brosseau, Cook and Zalcman. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Nowak, Anna K.
Brosseau, Solenn
Cook, Alistair
Zalcman, Gérard
Antiangiogeneic Strategies in Mesothelioma
title Antiangiogeneic Strategies in Mesothelioma
title_full Antiangiogeneic Strategies in Mesothelioma
title_fullStr Antiangiogeneic Strategies in Mesothelioma
title_full_unstemmed Antiangiogeneic Strategies in Mesothelioma
title_short Antiangiogeneic Strategies in Mesothelioma
title_sort antiangiogeneic strategies in mesothelioma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040194/
https://www.ncbi.nlm.nih.gov/pubmed/32133285
http://dx.doi.org/10.3389/fonc.2020.00126
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