| First Author | Shamseddine A | Year | 2023 |
| Journal | J Exp Med | Volume | 220 |
| Issue | 3 | PubMed ID | 36534085 |
| Mgi Jnum | J:334048 | Mgi Id | MGI:7438030 |
| Doi | 10.1084/jem.20220809 | Citation | Shamseddine A, et al. (2023) Innate immune signaling drives late cardiac toxicity following DNA-damaging cancer therapies. J Exp Med 220(3) |
| abstractText | 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. |
