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Hypoxia, metabolism, and the circadian clock: new links to overcome radiation resistance in high-grade gliomas

Radiotherapy is the cornerstone of treatment of high-grade gliomas (HGGs). It eradicates tumor cells by inducing oxidative stress and subsequent DNA damage. Unfortunately, almost all HGGs recur locally within several months secondary to radioresistance with intricate molecular mechanisms. Therefore,...

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Autores principales: Shen, Han, Cook, Kristina, Gee, Harriet E., Hau, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339573/
https://www.ncbi.nlm.nih.gov/pubmed/32631383
http://dx.doi.org/10.1186/s13046-020-01639-2
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author Shen, Han
Cook, Kristina
Gee, Harriet E.
Hau, Eric
author_facet Shen, Han
Cook, Kristina
Gee, Harriet E.
Hau, Eric
author_sort Shen, Han
collection PubMed
description Radiotherapy is the cornerstone of treatment of high-grade gliomas (HGGs). It eradicates tumor cells by inducing oxidative stress and subsequent DNA damage. Unfortunately, almost all HGGs recur locally within several months secondary to radioresistance with intricate molecular mechanisms. Therefore, unravelling specific underlying mechanisms of radioresistance is critical to elucidating novel strategies to improve the radiosensitivity of tumor cells, and enhance the efficacy of radiotherapy. This review addresses our current understanding of how hypoxia and the hypoxia-inducible factor 1 (HIF-1) signaling pathway have a profound impact on the response of HGGs to radiotherapy. In addition, intriguing links between hypoxic signaling, circadian rhythms and cell metabolism have been recently discovered, which may provide insights into our fundamental understanding of radioresistance. Cellular pathways involved in the hypoxic response, DNA repair and metabolism can fluctuate over 24-h periods due to circadian regulation. These oscillatory patterns may have consequences for tumor radioresistance. Timing radiotherapy for specific times of the day (chronoradiotherapy) could be beneficial in patients with HGGs and will be discussed.
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spelling pubmed-73395732020-07-09 Hypoxia, metabolism, and the circadian clock: new links to overcome radiation resistance in high-grade gliomas Shen, Han Cook, Kristina Gee, Harriet E. Hau, Eric J Exp Clin Cancer Res Review Radiotherapy is the cornerstone of treatment of high-grade gliomas (HGGs). It eradicates tumor cells by inducing oxidative stress and subsequent DNA damage. Unfortunately, almost all HGGs recur locally within several months secondary to radioresistance with intricate molecular mechanisms. Therefore, unravelling specific underlying mechanisms of radioresistance is critical to elucidating novel strategies to improve the radiosensitivity of tumor cells, and enhance the efficacy of radiotherapy. This review addresses our current understanding of how hypoxia and the hypoxia-inducible factor 1 (HIF-1) signaling pathway have a profound impact on the response of HGGs to radiotherapy. In addition, intriguing links between hypoxic signaling, circadian rhythms and cell metabolism have been recently discovered, which may provide insights into our fundamental understanding of radioresistance. Cellular pathways involved in the hypoxic response, DNA repair and metabolism can fluctuate over 24-h periods due to circadian regulation. These oscillatory patterns may have consequences for tumor radioresistance. Timing radiotherapy for specific times of the day (chronoradiotherapy) could be beneficial in patients with HGGs and will be discussed. BioMed Central 2020-07-07 /pmc/articles/PMC7339573/ /pubmed/32631383 http://dx.doi.org/10.1186/s13046-020-01639-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Shen, Han
Cook, Kristina
Gee, Harriet E.
Hau, Eric
Hypoxia, metabolism, and the circadian clock: new links to overcome radiation resistance in high-grade gliomas
title Hypoxia, metabolism, and the circadian clock: new links to overcome radiation resistance in high-grade gliomas
title_full Hypoxia, metabolism, and the circadian clock: new links to overcome radiation resistance in high-grade gliomas
title_fullStr Hypoxia, metabolism, and the circadian clock: new links to overcome radiation resistance in high-grade gliomas
title_full_unstemmed Hypoxia, metabolism, and the circadian clock: new links to overcome radiation resistance in high-grade gliomas
title_short Hypoxia, metabolism, and the circadian clock: new links to overcome radiation resistance in high-grade gliomas
title_sort hypoxia, metabolism, and the circadian clock: new links to overcome radiation resistance in high-grade gliomas
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339573/
https://www.ncbi.nlm.nih.gov/pubmed/32631383
http://dx.doi.org/10.1186/s13046-020-01639-2
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