ArticleNature communications2023
Increased glucose availability sensitizes pancreatic cancer to chemotherapy.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23citing papers in PubMed
7.8field-weighted citation impact, top 2% of its field
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Flavokawain A inhibits high glucose-induced malignant progression of lung cancer cells by suppressing PRMT5-mediated PTEN neddylation and nuclear translocation.Oncology letters · 2026Article
- Glucose-containing carriers in cancer therapy (GLUCOSE-ONC): A multistream critical review and quantitative exposure framework.Neoplasia (New York, N.Y.) · 2026Review
- Diabetes and cancer: glucose control impact on survival and tumor outcomes.Reviews in endocrine & metabolic disorders · 2026Review
- Genotypic and Phenotypic Diversity as a Function of CRISPR-Directed Gene Knock-Out ofBiomolecules · 2026Article
- Increased Glucose Availability Sensitizes Pancreatic Cancer to Macrophage-Targeting Immunotherapies.Cancer research communications · 2026Article
- A ketogenic diet sensitizes pancreatic cancer to glutamine metabolism inhibitors.Cell reports. Medicine · 2026Article
- Glucose‑driven TRIB3 enhances the tumorigenic potential of colon cancer via the PI3K/AKT pathway.Molecular medicine reports · 2026Article
- Impact of diabetes mellitus on treatment efficacy in patients with advanced pancreatic cancer: the Italian, multicenter, observational PANCAKE study.ESMO gastrointestinal oncology · 2026Article
- Enhancing cancer susceptibility to disulfidptosis by inducing cell cycle arrest and impairing DNA repair.Theranostics · 2026Article
- Research progress on the etiology and pathogenesis of pancreatic cancer: a narrative review.Frontiers in oncology · 2026Review
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- A prognostic signature based on insulin-signaling-pathway genes for hepatocellular carcinoma.Discover oncology · 2025Article
- What's on the menu?: metabolic constraints in the pancreatic tumor microenvironment.The Journal of clinical investigation · 2025Review
- The perspective of targeting cancer cell metabolism: combination therapy approaches.Molecular biology reports · 2025Review
- Potential of Proliferative Markers in Pancreatic Cancer Management: A Systematic Review.Health science reports · 2025Review
- Integrated molecular and microenvironmental drivers of drug resistance in gastrointestinal cancers: mechanisms, immunotherapy challenges, and precision strategies.Frontiers in oncology · 2025Review
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- Fast-relaxing hydrogels with reversibly tunable mechanics for dynamic cancer cell culture.Biomaterials advances · 2024Article
- Regulation of antioxidants in cancer.Molecular cell · 2024Review
- miRNA signatures underlie chemoresistance in the gemcitabine-resistant pancreatic ductal adenocarcinoma cell line MIA PaCa-2 GR.Frontiers in genetics · 2024Article
Corrections and comments
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Authors and funding
27 authors at 9 institutions in 1 country.
Ali Vaziri-GoharCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA. avaziri1@luc.edu.ORCID 0000-0002-6924-8691
Jonathan J HueDepartment of Surgery, Division of Surgical Oncology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA.
Ata AbbasCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.ORCID 0000-0001-8272-1853
Hallie J GraorCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Omid HajihassaniCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Mehrdad ZareiCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.ORCID 0000-0003-0127-1489
George TitomihelakisJefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
John FeczkoDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
Moeez RathoreCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Sylwia ChelstowskaCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Alexander W LoftusDepartment of Surgery, Division of Surgical Oncology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA.
Rui WangCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Mahsa ZareiDepartment of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
Maryam GoudarziProteomics and Metabolomics Core, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0003-4961-3935
Renliang ZhangProteomics and Metabolomics Core, Cleveland Clinic, Cleveland, OH, USA.
Belinda WillardProteomics and Metabolomics Core, Cleveland Clinic, Cleveland, OH, USA.
Li ZhangDepartment of Molecular and Integrative Physiology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Adam KresakCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Joseph E WillisDepartment of Pathology, Case Western Reserve University and Department of Pathology Cleveland Medical Center, Cleveland, OH, USA.
Gi-Ming WangDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Curtis TatsuokaDepartment of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
Joseph M SalvinoMolecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.ORCID 0000-0002-2184-5980
Ilya BedermanDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
Henri BrunengraberDepartment of Nutrition and Biochemistry, Case Western Reserve University, Cleveland, OH, USA.
Costas A LyssiotisDepartment of Molecular and Integrative Physiology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Jonathan R BrodyBrenden Colson Center for Pancreatic Care; Departments of Surgery and Cell, Developmental & Cancer Biology; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Jordan M WinterCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA. jordan.winter@UHhospitals.org.ORCID 0000-0002-5200-6557
Case Western Reserve University · USUniversity Hospitals of Cleveland · USCleveland Clinic · USLoyola University Chicago · USMichigan Medicine · USOregon Health & Science University · USThe Wistar Institute · USThomas Jefferson University · USUniversity of Pittsburgh · US
Funding
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2MTUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI Amar Desai · 1987 to 2026
$142.3MTumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9MUnderstanding the origins of rapid recurrence of pancreatic cancer after resectionP30CA069533 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Grace B Gill · 1997 to 2026
$60.5MTargeting 15-PGDH in Colon Cancer Prognosis, Prediction, Treatment and PreventionP50CA150964 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARKOWITZ, SANFORD D. · 2011 to 2022
$24.6MDynamic Metabolomics via Isotopomer Analysis(RMI)R33DK070291 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI BRUNENGRABER, HENRI · 2004 to 2006
$3.3MMechanisms of metabolic reprogramming by PIK3CA oncogenic mutationsR01CA196643 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI Zhenghe Wang · 2016 to 2026
$3.1MComparative analysis between patient-derived models of pancreatic ductal adenocarcinomas and matched tumor specimensU01CA224012 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI BRODY, JONATHAN, COUSSENS, LISA M. · 2019 to 2023
$2.9MTargeting pancreatic cancer's metabolic addiction to HuRR37CA227865 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI WINTER, JORDAN M · 2018 to 2024
$2.7MIntratumoral Metabolic Crosstalk Promotes Therapeutic Resistance in Pancreatic CancerR37CA237421 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Costas Andreas Lyssiotis · 2020 to 2026
$2.6MOptimizing anti-wild-type IDH1 therapy in pancreatic cancerR01CA287672 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI Jonathan Brody, Jordan M Winter · 2024 to 2026
$2.0MStromal metabolism promotes therapeutic resistance in pancreatic cancerR01CA248160 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LYSSIOTIS, COSTAS ANDREAS · 2020 to 2024
$2.0MNCI NIH HHS F32 CA247466NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA043703NCI NIH HHS P30 CA046592NCI NIH HHS P30 CA069533NCI NIH HHS P50 CA150964NCI NIH HHS R00 CA225756NCI NIH HHS R01 CA196643NCI NIH HHS R01 CA212600NCI NIH HHS R01 CA244931NCI NIH HHS R01 CA248160NCI NIH HHS R01 CA287672NCI NIH HHS R21 CA173605NCI NIH HHS R21 CA263996NCI NIH HHS R37 CA227865NCI NIH HHS R37 CA237421NCI NIH HHS U01 CA224012NIDDK NIH HHS R33 DK070291NIH HHS S10 OD030245
Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies the suppressive effect of forced hyperglycemia in mouse models of PDAC, while rescuing this pathway mitigates anti-tumor effects observed with chemotherapy and high glucose.
Indexed as
Carcinoma, Pancreatic DuctalPancreatic NeoplasmsAdministration, CutaneousAnimalsGlucoseMiceGlucose
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