ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Unbiased Metabolic Profiling Predicts Sensitivity of High MYC-Expressing Atypical Teratoid/Rhabdoid Tumors to Glutamine Inhibition with 6-Diazo-5-Oxo-L-Norleucine.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. 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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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- The CoREST complex inhibitor, corin, decreases tumor growth, increases cellular differentiation and extends lifespan in ATRT xenograft models.Neuro-oncology · 2026Article
- Protocol for Seahorse 3D Mito Stress assay in patient-derived atypical teratoid rhabdoid tumor CHLA-05-ATRT single neurospheres.STAR protocols · 2026Article
- Decoding the Hexosamine Biosynthesis Pathway: Implications for Novel Therapeutic Strategies in Sarcoma.Journal of cellular physiology · 2026Review
- Protocol for Seahorse 3D Mito Stress assay in patient-derived pediatric brain tumor single neurospheres.bioRxiv : the preprint server for biology · 2025Article
- Designing a time-dependent therapeutic strategy using CDK4/6 inhibitors in an intracranial ATRT model.Neuro-oncology · 2025Article
- Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors.Cell reports. Medicine · 2025Article
- Case report: Molecular characterization of adult atypical teratoid rhabdoid tumor and review of the literature.Frontiers in oncology · 2025Article
- Establishment and Characterization of Three Human Ocular Adnexal Sebaceous Carcinoma Cell Lines.International journal of molecular sciences · 2024Article
- Roles of Glutathione and AP-1 in the Enhancement of Vitamin D-Induced Differentiation by Activators of the Nrf2 Signaling Pathway in Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2024Article
- Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma.Nature cancer · 2024Article
- Pro-905, a Novel Purine Antimetabolite, Combines with Glutamine Amidotransferase Inhibition to Suppress Growth of Malignant Peripheral Nerve Sheath Tumor.Molecular cancer therapeutics · 2023Article
- The opportunities and challenges for nutritional intervention in childhood cancers.Frontiers in nutrition · 2023Review
- Human Malignant Rhabdoid Tumor Antigens as Biomarkers and Potential Therapeutic Targets.Cancers · 2022Article
- Molecular targeted therapies for pediatric atypical teratoid/rhabdoid tumors.Pediatric investigation · 2022Review
- Dual mTORC1/2 inhibition compromises cell defenses against exogenous stress potentiating Obatoclax-induced cytotoxicity in atypical teratoid/rhabdoid tumors.Cell death & disease · 2022Article
- Integrated analysis of bulk and single-cell RNA-seq reveals the role of MYC signaling in lung adenocarcinoma.Frontiers in genetics · 2022Article
- Molecular Heterogeneity in Pediatric Malignant Rhabdoid Tumors in Patients With Multi-Organ Involvement.Frontiers in oncology · 2022Article
- TORC1/2 kinase inhibition depletes glutathione and synergizes with carboplatin to suppress the growth of MYC-driven medulloblastoma.Cancer letters · 2021Article
- Gluconeogenic enzyme PCK1 deficiency promotes CHK2 O-GlcNAcylation and hepatocellular carcinoma growth upon glucose deprivation.The Journal of clinical investigation · 2021Article
- Glutamine Antagonist GA-607 Causes a Dramatic Accumulation of FGAR which can be used to Monitor Target Engagement.Current drug metabolism · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAtypical teratoid/rhabdoid tumors (AT/RT) are aggressive infantile brain tumors with poor survival. Recent advancements have highlighted significant molecular heterogeneity in AT/RT with an aggressive subgroup featuring overexpression of the EXPERIMENTAL
designMetabolites were extracted from AT/RT cell lines and separated in ultra-high performance liquid chromatography mass spectrometry. Glutamine metabolic inhibition with 6-diazo-5-oxo-L-norleucine (DON) was tested with growth and cell death assays and survival studies in orthotopic mouse models of AT/RT. Metabolic flux analysis was completed to identify combination therapies to act synergistically to improve survival in high MYC AT/RT.
resultsUnbiased metabolic profiling of AT/RT cell models identified a unique dependence of high MYC AT/RT on glutamine for survival. The glutamine analogue, DON, selectively targeted high MYC cell lines, slowing cell growth, inducing apoptosis, and extending survival in orthotopic mouse models of AT/RT. Metabolic flux experiments with isotopically labeled glutamine revealed DON inhibition of glutathione (GSH) synthesis. DON combined with carboplatin further slowed cell growth, induced apoptosis, and extended survival in orthotopic mouse models of high MYC AT/RT.
conclusionsUnbiased metabolic profiling of AT/RT identified susceptibility of high MYC AT/RT to glutamine metabolic inhibition with DON therapy. DON inhibited glutamine-dependent synthesis of GSH and synergized with carboplatin to extend survival in high MYC AT/RT. These findings can rapidly translate into new clinical trials to improve survival in high MYC AT/RT.
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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 OpenQuestion graph.