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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Bibliographic Details
Published in:Journal of experimental & clinical cancer research 2020-07, Vol.39 (1), p.129-14, Article 129
Main Authors: Shen, Han, Cook, Kristina, Gee, Harriet E, Hau, Eric
Format: Article
Language:English
Subjects:
Adaptation
Apoptosis
Cancer therapies
Care and treatment
Cell cycle
Cell growth
Circadian Clocks
Circadian rhythm
Deoxyribonucleic acid
DNA
DNA damage
Enzymes
Gene expression
Glioma
Glioma - metabolism
Glioma - pathology
Glioma - radiotherapy
Gliomas
Glucose
High-grade glioma
Humans
Hypoxia
Magnetic resonance imaging
Medical prognosis
Metabolism
Neoplasm Recurrence, Local - prevention & control
Pediatrics
Physiological aspects
Radiation
Radiation therapy
Radiation Tolerance
Radiotherapy
Review
Signal Transduction
Stem cells
Tumors
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Summary: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.
ISSN:1756-9966
0392-9078
1756-9966
DOI:10.1186/s13046-020-01639-2