ArticleCancer cell2025
Isocitrate dehydrogenase 1 primes group-3 medulloblastomas for cuproptosis.
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Article in Cancer cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15citing papers in PubMed
–field-weighted citation impact
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Who cites it
15 citing papers in PubMed.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- A Self-Monitoring Single-Atom Copper Nanocapsule for Cascade-Responsive Tumor Cuproptosis Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- Article
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- From copper imbalance to immunometabolic remodeling: cuproptosis-related vulnerability and therapeutic hypotheses in autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- PCK2 as a potential therapeutic target for aggressive MYC-amplified non-WNT/non-SHH medulloblastoma based on tumor continuum.Acta neuropathologica communications · 2026Article
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- LncRNA-HLX-2-7/HLX axis-dependent metabolic reprogramming drives cancer progression in group 3 medulloblastoma.Acta neuropathologica communications · 2026Article
- Medulloblastoma stem cell programs: Molecular roadmaps of disease progression.Developmental cell · 2026Review
- Metabolic-Immune Reprogramming via CuZnS@BSA Nanoregulators to Overcome Resistance in Triple-Negative Breast Cancer.Theranostics · 2026Article
- Roles of cuproptosis in central nervous system tumors: from molecular mechanisms to therapeutic prospects.Frontiers in cell and developmental biology · 2026Review
- Exploiting metabolic cell death for cancer therapy.Nature reviews. Cancer · 2026Review
- Single-cell multi-omics identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma.Nature communications · 2025Article
- Narciclasine as a Novel Treatment for Lung Cancer and Malignant Pleural Mesothelioma: Insights from 3D Tumor Spheroid Models.International journal of molecular sciences · 2025Article
- Glutamine antagonism suppresses tumor growth in adrenocortical carcinoma through inhibition of de novo nucleotide biosynthesis.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
45 authors.
Derek DangLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Akash DeogharkarLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
John McKolayLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Kyle S SmithDepartment of Developmental Neurobiology, Neurobiology and Brain Tumor Program, St. Jude Children's Research Hospital, Memphis, TN, USA; Center of Excellence in Neuro-Oncology Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
Pooja PanwalkarLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Simon HoffmanLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Wentao TianLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Sunjong JiDepartment of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA.
Ana P AzambujaDepartment of Pathology, Boston Children's Hospital, Boston, MA, USA; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Siva Kumar NatarajanLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Joanna LumLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Jill BaylissLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Katie ManzeckLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Stefan R SwehaLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Erin HamanishiLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Matthew PunLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Diya PatelLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Sagar RauLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Olamide AnimasahunDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA; Laboratory for Systems Biology of Human Diseases, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Abhinav AchrejaLaboratory for Systems Biology of Human Diseases, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Martin P OgrodzinskiDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Jutta DiesslDepartment of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Jennifer CotterDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Debra HawesDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Fusheng YangDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Robert DohertyDepartment of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA.
Andrea T FransonDepartment of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA.
Allison R HanafordDepartment of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Division of Neuropathology, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Charles G EberhartDepartment of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Division of Neuropathology, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Eric H RaabeSidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Division of Pediatric Oncology, Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Brent A OrrDivision of Neuropathology, Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
Robert J Wechsler-ReyaCancer Genome and Epigenetics Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA; Department of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
Brandon ChenDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Costas A LyssiotisRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Yatrik M ShahRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Sophia Y LuntDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA; Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI, USA.
Ruma BanerjeeDepartment of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Alexander R JudkinsDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
John R PrensnerDepartment of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Carl KoschmannDepartment of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Sebastian M WaszakLaboratory of Computational Neuro-Oncology, Swiss Institute for Experimental Cancer Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Deepak NagrathDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA; Laboratory for Systems Biology of Human Diseases, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Marcos Simoes-CostaDepartment of Pathology, Boston Children's Hospital, Boston, MA, USA; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Paul A NorthcottDepartment of Developmental Neurobiology, Neurobiology and Brain Tumor Program, St. Jude Children's Research Hospital, Memphis, TN, USA; Center of Excellence in Neuro-Oncology Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
Sriram VennetiLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA. Electronic address: svenneti@med.umich.edu.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MMICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3MThe DNA Damage Response and Tumorigenesis in the BrainP01CA096832 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BAKER, SUZANNE J. · 2003 to 2025
$38.0MGenetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4MSulfide Oxidation and SignalingR35GM130183 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RUMA V BANERJEE · 2019 to 2026
$3.6MIdentifying and Targeting the Drivers of Pediatric Brain TumorsR35NS122339 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Robert J. Wechsler-Reya · 2021 to 2026
$3.6MTargeting integrated metabolic and epigenetic pathways in childhood ependymomasR01CA261926 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Deepak Nagrath, Benita Tamrazi · 2022 to 2026
$3.0MUnravelling metabolic dependencies in H3K27M mutant DIPGR01NS110572 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Venneti · 2019 to 2026
$2.7MTargeting EGFR/FOXG1-mediated resistance to ONC201 in H3K27M-mutant diffuse midline gliomaR01NS124607 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Carl J Koschmann · 2022 to 2026
$2.2MExamining PHGDH-mediated activation of sialic acid metabolism to drive triple-negative breast cancer metastasisR01CA270136 · NCI · MICHIGAN STATE UNIVERSITY · PI Sophia Lunt · 2022 to 2026
$2.0MThe role of ATRX mutation in the epigenetic dysregulation of cell cycle in pediatric high-grade gliomaR01NS119231 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOSCHMANN, CARL J · 2021 to 2025
$1.9MTargeting metabolic dependencies in ZFTA-RELA fusion childhood ependymomasR01NS127799 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Venneti · 2023 to 2026
$1.8MNCI NIH HHS F31 CA260935NCI NIH HHS K08 CA263552NCI NIH HHS P01 CA096832NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA261926NCI NIH HHS R01 CA270136NICHD NIH HHS P50 HD105351NIEHS NIH HHS R01 ES030695NIGMS NIH HHS R35 GM130183NIGMS NIH HHS T32 GM007863NINDS NIH HHS R01 NS110572NINDS NIH HHS R01 NS119231NINDS NIH HHS R01 NS124607NINDS NIH HHS R01 NS127799NINDS NIH HHS R35 NS122339
Abstract
MYC-driven group-3 medulloblastomas (MBs) are malignant pediatric brain cancers without cures. To define actionable metabolic dependencies, we identify upregulation of dihydrolipoyl transacetylase (DLAT), the E2-subunit of pyruvate dehydrogenase complex (PDC) in a subset of group-3 MB with poor prognosis. DLAT is induced by c-MYC and targeting DLAT lowers TCA cycle metabolism and glutathione synthesis. We also note upregulation of isocitrate dehydrogenase 1 (IDH1) gene expression in group-3 MB patient tumors and suppression of IDH1 epigenetically reduces c-MYC and downstream DLAT levels in multiple c-MYC amplified cancers. DLAT is a central regulator of cuproptosis (copper-dependent cell death) induced by the copper ionophore elesclomol. DLAT expression in group-3 MB cells correlates with increased sensitivity to cuproptosis. Elesclomol is brain-penetrant and suppresses tumor growth in vivo in multiple group-3 MB animal models. Our data uncover an IDH1/c-MYC dependent vulnerability that regulates DLAT levels and can be targeted to kill group-3 MB by cuproptosis.
Indexed as
Cerebellar NeoplasmsIsocitrate DehydrogenaseMedulloblastomaAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansHydrazinesMiceProto-Oncogene Proteins c-mycXenograft Model Antitumor AssaysHydrazinesIDH1 protein, humanIsocitrate DehydrogenaseMYC protein, humanProto-Oncogene Proteins c-myccancer metabolismcell deathcoppercuproptosiselesclomolepigeneticspediatric brain tumorprotein lipoylation
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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 Socratic graph.