ArticleNature cancer2024
Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma.
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 59 papers.
What it found
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Who cites it
59 citing papers in PubMed, 54 citations in OpenAlex.
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Article
- 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
- Endogenous metabolite signaling orchestrates tumor immune evasion.Cell insight · 2026Review
- Rewiring glucose metabolism in pancreatic cancer by natural compounds: implications for immune evasion and therapeutic targets.Molecular biology reports · 2026Review
- The MAPK/ATF3/ASNS axis drives amino acid metabolic reprogramming to promote NSCLC survival under glucose deprivation.Journal of translational medicine · 2026Article
- Reprogramming macrophage immunometabolism via glutamine antagonism potentiates colorectal cancer therapy in mice.Nature communications · 2026Article
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- A ketogenic diet sensitizes pancreatic cancer to glutamine metabolism inhibitors.Cell reports. Medicine · 2026Article
- Decoding the Hexosamine Biosynthesis Pathway: Implications for Novel Therapeutic Strategies in Sarcoma.Journal of cellular physiology · 2026Review
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- PHGDH is a targetable driver of PDAC progression.bioRxiv : the preprint server for biology · 2026Article
- Macropinocytosis and Vascularization Determine Response to mTOR Inhibitors in Lung Squamous Cell Carcinoma.Cancer research · 2026Article
- GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Asparagine depletion mediates high-intensity exercise induced cardiac injury: translational evidence from metabolomics and Mendelian randomization.European journal of applied physiology · 2026Article
- The Aging Microenvironment Is a Determinant of Immune Exclusion and Metastatic Fate in Pancreatic Cancer.Cancer research · 2026Article
- Suppression of ASNS expression by VHL-mediated ubiquitination hinders the progression of renal cell carcinoma through enhancing JUP expression and inhibiting PI3K-AKT and MAPK pathways.International journal of biological sciences · 2026Article
- Structural reassignment of compound 968, an allosteric glutaminase inhibitor.Beilstein journal of organic chemistry · 2026Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
In pancreatic ductal adenocarcinoma (PDAC), glutamine is a critical nutrient that drives a wide array of metabolic and biosynthetic processes that support tumor growth. Here, we elucidate how 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist that broadly inhibits glutamine metabolism, blocks PDAC tumor growth and metastasis. We find that DON significantly reduces asparagine production by inhibiting asparagine synthetase (ASNS), and that the effects of DON are rescued by asparagine. As a metabolic adaptation, PDAC cells upregulate ASNS expression in response to DON, and we show that ASNS levels are inversely correlated with DON efficacy. We also show that L-asparaginase (ASNase) synergizes with DON to affect the viability of PDAC cells, and that DON and ASNase combination therapy has a significant impact on metastasis. These results shed light on the mechanisms that drive the effects of glutamine mimicry and point to the utility of cotargeting adaptive responses to control PDAC progression.
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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.