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Innate immune signaling drives late cardiac toxicity following DNA-damaging cancer therapies.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2023 Mar 06; Vol. 220 (3). Date of Electronic Publication: 2022 Dec 19. - Publication Year :
- 2023
-
Abstract
- Late cardiac toxicity is a potentially lethal complication of cancer therapy, yet the pathogenic mechanism remains largely unknown, and few treatment options exist. Here we report DNA-damaging agents such as radiation and anthracycline chemotherapies inducing delayed cardiac inflammation following therapy due to activation of cGAS- and STING-dependent type I interferon signaling. Genetic ablation of cGAS-STING signaling in mice inhibits DNA damage-induced cardiac inflammation, rescues late cardiac functional decline, and prevents death from cardiac events. Treatment with a STING antagonist suppresses cardiac interferon signaling following DNA-damaging therapies and effectively mitigates cardiac toxicity. These results identify a therapeutically targetable, pathogenic mechanism for one of the most vexing treatment-related toxicities in cancer survivors.<br /> (© 2022 Shamseddine et al.)
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 220
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 36534085
- Full Text :
- https://doi.org/10.1084/jem.20220809