Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers.

doi:10.1038/s41467-025-62309-5

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Article

Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers.

Nature communications - 29 Jul 2025

Chabanon Roman M, Shcherbakova Liudmila, Lacroix-Triki Magali, Aglave Marine, Zeghondy Jean, Kriaa Victor, Gougé Antoine, Garrido Marlène, Edmond Elodie, Bigot Ludovic, Krastev Dragomir B, Brough Rachel, Pettitt Stephen J, Thomas-Bonafos Thibault, Samstein Robert, Massard Christophe, Deloger Marc, Tutt Andrew Nj, Barlesi Fabrice, Loriot Yohann, Delaloge Suzette, Tawk Marcel, Degerny Cindy, Lin Yea-Lih, Pistilli Barbara, Pasero Philippe, Lord Christopher J, Postel-Vinay Sophie

Abstract excerpt

ADAR1 is an RNA editing enzyme which prevents autoimmunity by blocking interferon responses triggered by cytosolic RNA sensors, and is a potential target in immuno-oncology. However, predictive biomarkers for ADAR1 inhibition are lacking. Using multiple in vitro and in vivo systems, we show that BRCA1/2 and ADAR1 are synthetically lethal, and that ADAR1 activity is upregulated in BRCA1/2-mutant cancers. ADAR1...

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PMID: 40730818
DOI: 10.1038/s41467-025-62309-5
PMCID: PMC12307730

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BRCA1

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