ArticleCell2024
Small-molecule GSDMD agonism in tumors stimulates antitumor immunity without toxicity.
Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Igniting antitumour immunity with cancer cell pyroptosis.Nature reviews. Cancer · 2026Review
- Mechanisms and therapeutic strategies of pyroptosis in sepsis‑induced acute lung injury (Review).International journal of molecular medicine · 2026Review
- Pyroptosis-Amplified Decoy Nanovesicles Orchestrate Pyroptotic Antigen Explosion and Endogenous Immune Revitalization for Potentiating Tumour Immunotherapy.Journal of extracellular vesicles · 2026Article
- A Molecular Trimming Strategy for Hypoxia-Tolerant Photosensitizers With Enhanced cGAS-STING Activation.Angewandte Chemie (International ed. in English) · 2026Article
- Article
- Evolution of botulinum neurotoxin serotype X proteases to induce inflammatory cell death in cancer cells.Nature biotechnology · 2026Article
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- A multi-level charged micelle-based microneedle transdermal system for immunosuppressive tumor microenvironment regulation and synergistic therapy.Materials today. Bio · 2026Article
- Engineering a 660 nm-Responsive Optogenetic Inducer of Pyroptosis for Precision Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Theme and variations: activation and regulation of gasdermin-mediated inflammation.Biochemical Society transactions · 2026Review
- Rewiring Pyroptosis to Potentiate Cancer Immunotherapy via a Gasdermin D Agonist Bypassing Caspase-3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pyroptosis-Inducing Engineered Microparticles for Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Gasdermin D antagonizes immunosuppression in prostate cancer by inducing LAMC2 degradation to block M2 macrophage polarization.Journal for immunotherapy of cancer · 2026Article
- Cell death pathways and targeting therapeutics in cancer therapy.Acta pharmacologica Sinica · 2026Review
- Targeting methionine-induced pyroptosis enhances anti-tumor immunity.Science China. Life sciences · 2026Article
- Chemotherapy-induced activation of caspase-1 and IL-1α release by cancer cells remotely skews myelopoiesis to drive pro tumorigenic systemic neutrophil-dominant inflammation.Nature communications · 2026Article
- Pyroptosis: Turning Up the Heat on Cancer.Annual review of immunology · 2026Review
- The dual role of pyroptosis in prostate cancer: new perspectives from molecular mechanisms to clinical translation.Molecular biology reports · 2026Review
- Pan-membrane pyroptosis of liver induced by gasdermin-encoding mRNAs.National science review · 2026Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Gasdermin-mediated inflammatory cell death (pyroptosis) can activate protective immunity in immunologically cold tumors. Here, we performed a high-throughput screen for compounds that could activate gasdermin D (GSDMD), which is expressed widely in tumors. We identified 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB) as a direct and selective GSDMD agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD. In mouse tumor models, pulsed and low-level pyroptosis induced by DMB suppresses tumor growth without harming GSDMD-expressing immune cells. Protection is immune-mediated and abrogated in mice lacking lymphocytes. Vaccination with DMB-treated cancer cells protects mice from secondary tumor challenge, indicating that immunogenic cell death is induced. DMB treatment synergizes with anti-PD-1. DMB treatment does not alter circulating proinflammatory cytokine or leukocyte numbers or cause weight loss. Thus, our studies reveal a strategy that relies on a low level of tumor cell pyroptosis to induce antitumor immunity and raise the possibility of exploiting pyroptosis without causing overt toxicity.
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Registered trials
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.