ArticleCell reports. Medicine2025
Targeting pancreatic cancer glutamine dependency confers vulnerability to GPX4-dependent ferroptosis.
Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Glutamine-restricted diets restore sensitivity to KRASCell reports. Medicine · 2026Article
- Integrative multi-omics analysis identifies a core ferroptosis signature and validates resveratrol as a novel inducer in pancreatic cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Metformin Induces Ferroptosis and Inhibits Malignant Progression in Diabetic Breast Cancer.Applied biochemistry and biotechnology · 2026Article
- CCDC6, a ferroptosis-related gene, modulates stemness features of pancreatic cancer cells in vitro.BMC cancer · 2026Article
- Circ-0030167/IGF2BP1 Induces Mitophagy-Mediated Ferroptosis via HMOX1 mRNA Stabilization in Pancreatic Cancer.Cancer science · 2026Article
- Metabolic orchestration driven by GGCT: diverting glutamine to glutathione biosynthesis while enhancing glucose anaplerosis for tumor proliferation.Cell death & disease · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- GPX4 Defines an Immune-Cold Phenotype and Poor Prognosis in Resected Lung Adenocarcinoma.Oncology research · 2026Article
- Obesity-induced metabolic reprogramming of the tumor immune microenvironment: mechanisms, spatial niches, and immunotherapy response.Frontiers in immunology · 2026Review
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- CT-based radiomics-clinical model for risk assessment of parenteral nutrition-associated hepatic steatosis in chronic intestinal failure and its metabolomic interpretation.Frontiers in nutrition · 2026Article
- Recent progress in understanding ferroptosis mechanisms in infectious diseases.Frontiers in cellular and infection microbiology · 2026Review
- Therapeutic targeting SPI1 in combination with erastin promotes ferroptosis in ccRCC.Communications biology · 2025Article
- Repurposing DPP-4 inhibitors as anticancer agents in KRAS-mutated pancreatic ductal adenocarcinoma.BMC pharmacology & toxicology · 2025Article
- AGR2 suppresses ferroptosis via the p53/FPN1 regulatory axis and drives therapeutic vulnerabilities in pancreatic cancer.Cell death & disease · 2025Article
- Review
- The interaction between ferroptosis and myocardial ischemia-reperfusion injury: molecular mechanisms and potential therapeutic targets.European journal of medical research · 2025Review
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) relies heavily on glutamine (Gln) utilization to meet its metabolic and biosynthetic needs. How epigenetic regulators contribute to the metabolic flexibility and PDAC's response and adaptation to Gln scarcity in the tumor milieu remains largely unknown. Here, we elucidate that prolonged Gln restriction or treatment with the Gln antagonist, 6-diazo-5-oxo-L-norleucine (DON), leads to growth inhibition and ferroptosis program activation in PDAC. A CRISPR-Cas9 screen identifies an epigenetic regulator, Paxip1, which promotes H3K4me3 upregulation and Hmox1 transcription upon DON treatment. Additionally, ferroptosis-related repressors (e.g., Slc7a11 and Gpx4) are increased as an adaptive response, thereby predisposing PDAC cells to ferroptosis upon Gln deprivation. Moreover, DON sensitizes PDAC cells to GPX4 inhibitor-induced ferroptosis, both in vitro and in patient-derived xenografts (PDXs). Taken together, our findings reveal that targeting Gln dependency confers susceptibility to GPX4-dependent ferroptosis via epigenetic remodeling and provides a combination strategy for PDAC therapy.
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