ArticleThe Journal of clinical investigation2024
Gasdermin C sensitizes tumor cells to PARP inhibitor therapy in cancer models.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The trial behind it
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Who cites it
32 citing papers in PubMed, 38 citations in OpenAlex.
- PARP inhibitors enhance antitumor immune responses by triggering pyroptosis via TNF-caspase 8-GSDMD/E axis in ovarian cancer.Journal for immunotherapy of cancer · 2024Trial
- Igniting antitumour immunity with cancer cell pyroptosis.Nature reviews. Cancer · 2026Review
- Theme and variations: activation and regulation of gasdermin-mediated inflammation.Biochemical Society transactions · 2026Review
- m6A-modified circFOXA1 promotes tumor immune evasion via enhancing PD-L1 deubiquitination in triple-negative breast cancer.Cytotechnology · 2026Article
- Pyroptosis: Turning Up the Heat on Cancer.Annual review of immunology · 2026Review
- Advances in the research of gasdermin-dependent pyroptosis mechanisms and therapeutic targets in inflammatory diseases.Apoptosis : an international journal on programmed cell death · 2026Review
- Leveraging PANoptosis-associated genes for unraveling implication of decidualization deficiency in pre-eclampsia via transcriptome data and experiment validation.Frontiers in cell and developmental biology · 2026Article
- Gasdermins in neurodegeneration: emerging mechanisms and therapeutic targets.Cell death & disease · 2025Review
- GSDME-dependent pyroptosis drives abdominal aortic aneurysm via promoting vascular senescence.Nature communications · 2025Article
- Disruption of heme homeostasis by nuclear receptor Nur77 induces pyroptosis through granzyme B-dependent GSDMC cleavage.Signal transduction and targeted therapy · 2025Article
- Targeting cell death pathways in acute myeloid leukemia: Molecular mechanisms and clinical implications (Review).Oncology reports · 2025Review
- Pyroptosis in cancer therapy: a double-edged sword for immune activation and tumor progression.Molecular cancer · 2025Review
- IRG1/itaconate/NRF2/GSH axis in tumor-associated macrophages drives therapy resistance and immune evasion in BRCA1-deficient breast cancer.bioRxiv : the preprint server for biology · 2025Article
- The deubiquitinase USP9X and E3 ligase WWP1 orchestrate IGF2BP2 ubiquitination homeostasis to drive TNBC progression and cisplatin sensitivity.Cell death & disease · 2025Article
- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapies.Bioactive materials · 2025Review
- Mechanistic insights into gasdermin-mediated pyroptosis.Nature reviews. Molecular cell biology · 2025Review
- Caspase-6/Gasdermin C-Mediated Tumor Cell Pyroptosis Promotes Colorectal Cancer Progression Through CXCL2-Dependent Recruitment of Myeloid-Derived Suppressor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PARP Inhibitors in the Neoadjuvant Setting; A Comprehensive Overview of the Rationale for their Use, Past and Ongoing Clinical Trials.Current oncology reports · 2025Review
- Novel clinical potential of poly (ADP‑ribose) polymerase inhibitors in triple‑negative breast cancer: Mechanistic insights and clinical applications (Review).Oncology letters · 2025Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved by FDA to treat cancer with BRCA mutations. BRCA mutations are considered to fuel a PARPi killing effect by inducing apoptosis. However, resistance to PARPi is frequently observed in the clinic due to an incomplete understanding on the molecular basis of PARPi function and a lack of good markers, beyond BRCA mutations, to predict response. Here, we show that gasdermin C (GSDMC) sensitized tumor cells to PARPi in vitro and in immunocompetent mice and caused durable tumor regression in an immune-dependent manner. A high expression level of GSDMC predicted better response to PARPi treatment in patients with triple-negative breast cancer (TNBC). PARPi treatment triggered GSDMC/caspase-8-mediated cancer cell pyroptosis (CCP) that enhanced PARPi killing of tumor cells. GSDMC-mediated CCP increased memory CD8+ T cell population in lymph node (LN), spleen, and tumor and, thus, promoted cytotoxic CD8+ T cell infiltration in the tumor microenvironment. T cell-derived granzyme B (GZMB) activated caspase-6, which subsequently cleaved GSDMC to induce pyroptosis. Interestingly, IFN-γ induced GSDMC expression, which, in turn, enhanced the cytotoxicity of PARPi and T cells. Importantly, GSDMC promoted tumor clearance independent of BRCA deficiency in multiple cancer types with PARPi treatment. This study identifies a general marker and target for PARPi therapy and offers insights into the mechanism of PARPi function.
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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.