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Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments

Pediatric high-grade gliomas (pHGG) are the leading cause of cancer-related death in children. These epigenetically dysregulated tumors often harbor mutations in genes encoding histone 3, which contributes to a stem cell-like, therapy-resistant phenotype. Furthermore, pHGG are characterized by a dif...

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Autores principales: Metselaar, Dennis S., du Chatinier, Aimée, Stuiver, Iris, Kaspers, Gertjan J. L., Hulleman, Esther
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047603/
https://www.ncbi.nlm.nih.gov/pubmed/33869066
http://dx.doi.org/10.3389/fonc.2021.662209
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author Metselaar, Dennis S.
du Chatinier, Aimée
Stuiver, Iris
Kaspers, Gertjan J. L.
Hulleman, Esther
author_facet Metselaar, Dennis S.
du Chatinier, Aimée
Stuiver, Iris
Kaspers, Gertjan J. L.
Hulleman, Esther
author_sort Metselaar, Dennis S.
collection PubMed
description Pediatric high-grade gliomas (pHGG) are the leading cause of cancer-related death in children. These epigenetically dysregulated tumors often harbor mutations in genes encoding histone 3, which contributes to a stem cell-like, therapy-resistant phenotype. Furthermore, pHGG are characterized by a diffuse growth pattern, which, together with their delicate location, makes complete surgical resection often impossible. Radiation therapy (RT) is part of the standard therapy against pHGG and generally the only modality, apart from surgery, to provide symptom relief and a delay in tumor progression. However, as a single treatment modality, RT still offers no chance for a cure. As with most therapeutic approaches, irradiated cancer cells often acquire resistance mechanisms that permit survival or stimulate regrowth after treatment, thereby limiting the efficacy of RT. Various preclinical studies have investigated radiosensitizers in pHGG models, without leading to an improved clinical outcome for these patients. However, our recently improved molecular understanding of pHGG generates new opportunities to (re-)evaluate radiosensitizers in these malignancies. Furthermore, the use of radio-enhancing agents has several benefits in pHGG compared to other cancers, which will be discussed here. This review provides an overview and a critical evaluation of the radiosensitization strategies that have been studied to date in pHGG, thereby providing a framework for improving radiosensitivity of these rapidly fatal brain tumors.
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spelling pubmed-80476032021-04-16 Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments Metselaar, Dennis S. du Chatinier, Aimée Stuiver, Iris Kaspers, Gertjan J. L. Hulleman, Esther Front Oncol Oncology Pediatric high-grade gliomas (pHGG) are the leading cause of cancer-related death in children. These epigenetically dysregulated tumors often harbor mutations in genes encoding histone 3, which contributes to a stem cell-like, therapy-resistant phenotype. Furthermore, pHGG are characterized by a diffuse growth pattern, which, together with their delicate location, makes complete surgical resection often impossible. Radiation therapy (RT) is part of the standard therapy against pHGG and generally the only modality, apart from surgery, to provide symptom relief and a delay in tumor progression. However, as a single treatment modality, RT still offers no chance for a cure. As with most therapeutic approaches, irradiated cancer cells often acquire resistance mechanisms that permit survival or stimulate regrowth after treatment, thereby limiting the efficacy of RT. Various preclinical studies have investigated radiosensitizers in pHGG models, without leading to an improved clinical outcome for these patients. However, our recently improved molecular understanding of pHGG generates new opportunities to (re-)evaluate radiosensitizers in these malignancies. Furthermore, the use of radio-enhancing agents has several benefits in pHGG compared to other cancers, which will be discussed here. This review provides an overview and a critical evaluation of the radiosensitization strategies that have been studied to date in pHGG, thereby providing a framework for improving radiosensitivity of these rapidly fatal brain tumors. Frontiers Media S.A. 2021-04-01 /pmc/articles/PMC8047603/ /pubmed/33869066 http://dx.doi.org/10.3389/fonc.2021.662209 Text en Copyright © 2021 Metselaar, du Chatinier, Stuiver, Kaspers and Hulleman https://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
Metselaar, Dennis S.
du Chatinier, Aimée
Stuiver, Iris
Kaspers, Gertjan J. L.
Hulleman, Esther
Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments
title Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments
title_full Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments
title_fullStr Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments
title_full_unstemmed Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments
title_short Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments
title_sort radiosensitization in pediatric high-grade glioma: targets, resistance and developments
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047603/
https://www.ncbi.nlm.nih.gov/pubmed/33869066
http://dx.doi.org/10.3389/fonc.2021.662209
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