Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown.
Cancer
Cancer systems biology
Mathematical biosciences
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
19 Nov 2021
19 Nov 2021
Historique:
received:
08
02
2021
revised:
01
09
2021
accepted:
25
10
2021
entrez:
26
11
2021
pubmed:
27
11
2021
medline:
27
11
2021
Statut:
epublish
Résumé
Cancer bioenergetics fuel processes necessary to maintain viability and growth under stress conditions. We hypothesized that cancer metabolism supports the repair of radiation-induced DNA double-stranded breaks (DSBs). We combined the systematic collection of metabolic and radiobiological data from a panel of irradiated cancer cell lines with mathematical modeling and identified a common metabolic response with impact on the DSB repair kinetics, including a mitochondrial shutdown followed by compensatory glycolysis and resumption of mitochondrial function. Combining ionizing radiation (IR) with inhibitors of the compensatory glycolysis or mitochondrial respiratory chain slowed mitochondrial recovery and DNA repair kinetics, offering an opportunity for therapeutic intervention. Mathematical modeling allowed us to generate new hypotheses on general and individual mechanisms of the radiation response with relevance to DNA repair and on metabolic vulnerabilities induced by cancer radiotherapy. These discoveries will guide future mechanistic studies for the discovery of metabolic targets for overcoming intrinsic or therapy-induced radioresistance.
Identifiants
pubmed: 34825138
doi: 10.1016/j.isci.2021.103366
pii: S2589-0042(21)01337-7
pmc: PMC8603201
doi:
Types de publication
Journal Article
Langues
eng
Pagination
103366Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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