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Adv."],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:p>Recent studies have described an ability of cancer cells to survive engagement of apoptotic pathways following chemical and therapeutic insults, challenging the prevailing model that caspase activation inevitably leads to cellular demise. Gasdermin E (GSDME), whose expression is frequently down-regulated or silenced in many tumors and tumor-derived cell lines, is a putative tumor suppressor capable of facilitating the induction of antitumor immunity. We found that GSDME expression precluded high caspase activity before cellular membrane rupture downstream of chemical and immune-mediated insults, and its absence allowed for enhanced activities downstream of caspase activation, including the DNA-damaging effects of caspase-activated deoxyribonuclease. Loss of GSDME allowed cells that had sustained DNA damage to survive, resulting in development and propagation of mutated clones. 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