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Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma
Diffuse intrinsic pontine glioma (DIPG) is a rare but highly lethal pediatric and adolescent tumor located in the pons of the brainstem. DIPGs harbor unique and specific pathological and molecular alterations, such as the hallmark lysine 27-to-methionine (H3K27M) mutation in histone H3, which lead t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9918797/ https://www.ncbi.nlm.nih.gov/pubmed/36724689 http://dx.doi.org/10.1016/j.neo.2023.100881 |
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author | Parsels, Leslie A. Wahl, Daniel R Koschmann, Carl Morgan, Meredith A. Zhang, Qiang |
author_facet | Parsels, Leslie A. Wahl, Daniel R Koschmann, Carl Morgan, Meredith A. Zhang, Qiang |
author_sort | Parsels, Leslie A. |
collection | PubMed |
description | Diffuse intrinsic pontine glioma (DIPG) is a rare but highly lethal pediatric and adolescent tumor located in the pons of the brainstem. DIPGs harbor unique and specific pathological and molecular alterations, such as the hallmark lysine 27-to-methionine (H3K27M) mutation in histone H3, which lead to global changes in the epigenetic landscape and drive tumorigenesis. While fractionated radiotherapy, the current standard of care, improves symptoms and delays tumor progression, DIPGs inevitably recur, and despite extensive efforts chemotherapy-driven radiosensitization strategies have failed to improve survival. Advances in our understanding of the role of epigenetics in the cellular response to radiation-induced DNA damage, however, offer new opportunities to develop combinational therapeutic strategies selective for DIPGs expressing H3K27M. In this review, we provide an overview of preclinical studies that explore potential radiosensitization strategies targeting the unique epigenetic landscape of H3K27M mutant DIPG. We further discuss opportunities to selectively radiosensitize DIPG through strategic inhibition of the radiation-induced DNA damage response. Finally, we discuss the potential for using radiation to induce anti-tumor immune responses that may be potentiated in DIPG by radiosensitizing-therapeutic strategies. |
format | Online Article Text |
id | pubmed-9918797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-99187972023-02-13 Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma Parsels, Leslie A. Wahl, Daniel R Koschmann, Carl Morgan, Meredith A. Zhang, Qiang Neoplasia Pediatric Brain Tumor Diffuse intrinsic pontine glioma (DIPG) is a rare but highly lethal pediatric and adolescent tumor located in the pons of the brainstem. DIPGs harbor unique and specific pathological and molecular alterations, such as the hallmark lysine 27-to-methionine (H3K27M) mutation in histone H3, which lead to global changes in the epigenetic landscape and drive tumorigenesis. While fractionated radiotherapy, the current standard of care, improves symptoms and delays tumor progression, DIPGs inevitably recur, and despite extensive efforts chemotherapy-driven radiosensitization strategies have failed to improve survival. Advances in our understanding of the role of epigenetics in the cellular response to radiation-induced DNA damage, however, offer new opportunities to develop combinational therapeutic strategies selective for DIPGs expressing H3K27M. In this review, we provide an overview of preclinical studies that explore potential radiosensitization strategies targeting the unique epigenetic landscape of H3K27M mutant DIPG. We further discuss opportunities to selectively radiosensitize DIPG through strategic inhibition of the radiation-induced DNA damage response. Finally, we discuss the potential for using radiation to induce anti-tumor immune responses that may be potentiated in DIPG by radiosensitizing-therapeutic strategies. Neoplasia Press 2023-01-30 /pmc/articles/PMC9918797/ /pubmed/36724689 http://dx.doi.org/10.1016/j.neo.2023.100881 Text en © 2023 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Pediatric Brain Tumor Parsels, Leslie A. Wahl, Daniel R Koschmann, Carl Morgan, Meredith A. Zhang, Qiang Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma |
title | Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma |
title_full | Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma |
title_fullStr | Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma |
title_full_unstemmed | Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma |
title_short | Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma |
title_sort | developing h3k27m mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma |
topic | Pediatric Brain Tumor |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9918797/ https://www.ncbi.nlm.nih.gov/pubmed/36724689 http://dx.doi.org/10.1016/j.neo.2023.100881 |
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