ArticleJCI insight2020
Caspase-8 loss radiosensitizes head and neck squamous cell carcinoma to SMAC mimetic-induced necroptosis.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- Intradermal priming to intravesical Bacillus Calmette-Guérin in non-muscle invasive bladder cancer: A translational research and phase I clinical trial.Oncology research · 2025Trial
- Review
- Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis.Nature communications · 2026Article
- Comparing and combining xevinapant with ATR and PARP inhibition for the radiosensitization of HPV-negative HNSCC cells.Scientific reports · 2026Article
- Review
- Bypassing the guardian: regulated cell death pathways in p53-mutant cancers.Cellular & molecular biology letters · 2025Review
- Identification of IGF2BP2 and long non-coding RNA TUG1 for the prognosis and tumour microenvironment in head and neck squamous cell carcinoma.Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale · 2025Article
- Advances in non-apoptotic regulated cell death: implications for malignant tumor treatment.Frontiers in oncology · 2025Review
- Complex IIa formation and ABC transporters determine sensitivity of OSCC to Smac mimetics.Cell death & disease · 2024Article
- High TNF and NF-κB Pathway Dependency Are Associated with AZD5582 Sensitivity in OSCC via CASP8-Dependent Apoptosis.Cancer research communications · 2024Article
- [Cisplatin promotes TNF-α autocrine to trigger RIP1/RIP3/MLKL-dependent necroptosis of human head and neck squamous cell carcinoma cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- Multifaceted Evaluation of Inhibitors of Anti-Apoptotic Proteins in Head and Neck Cancer: Insights from In Vitro, In Vivo, and Clinical Studies (Review).Pharmaceuticals (Basel, Switzerland) · 2024Review
- Reconstructing oral cavity tumor evolution through brush biopsy.Scientific reports · 2024Article
- Article
- Review
- Panoramic analysis of cell death patterns reveals prognostic and immune profiles of head and neck squamous cell carcinoma.American journal of cancer research · 2024Article
- Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma.Journal of biomedical science · 2023Review
- Histology Specific Molecular Biomarkers: Ushering in a New Era of Precision Radiation Oncology.Seminars in radiation oncology · 2023Review
- The expanding role of IAP antagonists for the treatment of head and neck cancer.Cancer medicine · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Caspase-8 (CASP8) is one of the most frequently mutated genes in head and neck squamous carcinomas (HNSCCs), and CASP8 mutations are associated with poor survival. The distribution of these mutations in HNSCCs suggests that they are likely to be inactivating. Inhibition of CASP8 has been reported to sensitize cancer cells to necroptosis, a regulated cell death mechanism. Here, we show that knockdown of CASP8 renders HNSCCs susceptible to necroptosis by a second mitochondria-derived activator of caspase (SMAC) mimetic, birinapant, in combination with pan-caspase inhibitors Z-VAD-FMK or emricasan and radiation. In a syngeneic mouse model of oral cancer, birinapant, particularly when combined with radiation, delayed tumor growth and enhanced survival under CASP8 loss. Exploration of molecular underpinnings of necroptosis sensitivity confirmed that the level of functional receptor-interacting serine/threonine protein kinase 3 (RIP3) determines susceptibility to this mode of death. Although an in vitro screen revealed that low RIP3 levels rendered many HNSCC cell lines resistant to necroptosis, patient tumors maintained RIP3 expression and should therefore remain sensitive. Collectively, these results suggest that targeting the necroptosis pathway with SMAC mimetics, especially in combination with radiation, may be relevant therapeutically in HNSCC with compromised CASP8 status, provided that RIP3 function is maintained.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.