ArticleNature cancer2024
Targeting pancreatic cancer metabolic dependencies through glutamine antagonism.
Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 103 citations in OpenAlex.
- A four‑gene signature identifies TKI‑induced persister cells and uncovers a ZLN005‑induced pyroptotic vulnerability via the GSDME pathway in EGFR‑mutant lung cancer.Molecular medicine reports · 2026Article
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- High-Density Type I Collagen Promotes IFN-γAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Recent advancements in NRF2-regulated ferroptosis modulation for targeted cancer therapy.Molecular biology reports · 2026Review
- Radiotherapy followed by metformin neoadjuvant therapy drives superior pancreatic cancer ferroptosis and augments anti-tumor immunity.Fundamental research · 2026Article
- Multi-omics integration identifiesTranslational andrology and urology · 2026Article
- The tumor microenvironment in pancreatic cancer: from composition to therapeutic targeting.Biochemical Society transactions · 2026Review
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Blocking L-carnitine synthesis by meldonium prolongs the survival in mice with pancreatic cancer.iScience · 2026Article
- Glutamine-restricted diets restore sensitivity to KRASCell reports. Medicine · 2026Article
- Rewiring glucose metabolism in pancreatic cancer by natural compounds: implications for immune evasion and therapeutic targets.Molecular biology reports · 2026Review
- 70 Years of DON and Beyond: Glutaminase Inhibition as a Synergistic Strategy in Cancer Combination Therapy.Pharmaceutics · 2026Review
- KRAS/ACTN4/p65-NR2A axis mediates glutamine-glutamate metabolic coupling between schwann cells and pancreatic cancer promoting perineural invasion.Journal of advanced research · 2026Article
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Metabolic characterization of the tumor microenvironment orchestrates therapeutic strategies and clinical outcomes in pancreatic cancer.Nature communications · 2026Article
- Functional Precision Oncology in Fibrolamellar Carcinoma: Ex Vivo Identification of Therapeutic Vulnerabilities.Cancers · 2026Article
- Metabolotheranostics of pancreatic cancer by targeting choline, glutamine, and glucose transporters with photoimmunotherapy.Npj imaging · 2026Article
- A ketogenic diet sensitizes pancreatic cancer to glutamine metabolism inhibitors.Cell reports. Medicine · 2026Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) cells use glutamine (Gln) to support proliferation and redox balance. Early attempts to inhibit Gln metabolism using glutaminase inhibitors resulted in rapid metabolic reprogramming and therapeutic resistance. Here, we demonstrated that treating PDAC cells with a Gln antagonist, 6-diazo-5-oxo-L-norleucine (DON), led to a metabolic crisis in vitro. In addition, we observed a profound decrease in tumor growth in several in vivo models using sirpiglenastat (DRP-104), a pro-drug version of DON that was designed to circumvent DON-associated toxicity. We found that extracellular signal-regulated kinase (ERK) signaling is increased as a compensatory mechanism. Combinatorial treatment with DRP-104 and trametinib led to a significant increase in survival in a syngeneic model of PDAC. These proof-of-concept studies suggested that broadly targeting Gln metabolism could provide a therapeutic avenue for PDAC. The combination with an ERK signaling pathway inhibitor could further improve the therapeutic outcome.
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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.