What this means
Scientists found that certain death signals help control which damaged cells become senescent. The work does not show whether this would help people or patients.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Human and mouse cells in lab dishes, plus some work in living mice
- Kind of research
- A study
The science
- Original title
- Death receptors regulate entry to therapy-induced senescence and orchestrate addiction to IAPs.
- Authors
- Gunay G, Hamsici S, Venugopalan V et al.
- Journal
- Science advances
- Published
- Oct 23, 2026
- Study type
- Study · in humans
- PMID
- 42912996 ↗
Abstract
Cytotoxic chemotherapy typically results in the elimination of a fraction of the tumor with surviving cells entering a state of persistence or premature replicative senescence that can lead to recurrence. Here, we show that therapy-induced senescence is associated with robust up-regulation of Fas and/or TRAIL-R2/DR5 death receptors in vitro and in vivo. The latter receptors restricted entry to senescence and exerted selective pressure on senescent cells through promoting assembly of proapoptotic receptor-interacting protein kinase 1 (RIPK1)/Fas-associated death domain protein (FADD)/Caspase-8 "FADDosome" complexes, restrained by cFLIPL. Accordingly, deletion of CASP-8 robustly enhanced entry to senescence and prolonged the life span of senescent cells. cIAP-2, which inhibits death receptor-driven cell death, was also up-regulated in senescent cells, and deletion of IAPs suppressed entry to senescence. Consistent with this, small-molecule IAP antagonists exhibited potent senolytic activity through enhancing death receptor-initiated Caspase-8 activation. Thus, death receptor-driven assembly of RIPK1/FADD/Caspase-8 complexes in senescent cells orchestrates addiction to IAPs that can be exploited by IAP antagonists.
Gunay G, Hamsici S, Venugopalan V et al. Death receptors regulate entry to therapy-induced senescence and orchestrate addiction to IAPs. Science advances. 2026. doi:10.1126/sciadv.aed4541. PMID: 42912996. https://pubmed.ncbi.nlm.nih.gov/42912996/
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