ArticleCell death discovery2020
A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity.
Article in Cell death discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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Who cites it
57 citing papers in PubMed, 87 citations in OpenAlex.
- Beyond Glycolysis: Targeting Non-Glycolytic Metabolic Pathways in Brain Tumors for Therapeutic Innovation: A Narrative Review.Health science reports · 2026Article
- Immunohistochemical evaluation of glutaminase-1 enzyme in oral squamous cell carcinoma.The Indian journal of medical research · 2026Article
- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- Targeting Metabolic Vulnerabilities in Glioblastoma: a Framework for Multi-node Combination Therapy.Current oncology reports · 2026Review
- Checkpoint inhibitor-associated pneumonitis in non-small cell lung cancer: a cohort study with transcriptomic analysis of inflammatory mechanisms.BMC pulmonary medicine · 2025Article
- Proteomics of malignant pleural mesothelioma under hypoxic and normoxic conditions in a large animal (porcine) tumor model.BMC cancer · 2025Article
- Metabolic Signature ofJournal of personalized medicine · 2025Review
- Glutaminase Expression in Canine Large-Cell Alimentary Lymphoma Cells and Effects of Glutaminase Inhibition by CB-839.Veterinary medicine and science · 2025Article
- Glutaminase-2 Expression Induces Metabolic Changes and Regulates Pyruvate Dehydrogenase Activity in Glioblastoma Cells.International journal of molecular sciences · 2025Article
- Metabolism of glioblastoma: a review of metabolic adaptations and metabolic therapeutic interventions.Frontiers in oncology · 2025Review
- The metabolic landscape of ovarian cancer stem cells: how do they survive?Frontiers in oncology · 2025Review
- Article
- Review
- Vitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures.International journal of molecular sciences · 2024Article
- Glutamine Metabolism Heterogeneity in Glioblastoma Unveils an Innovative Combination Therapy Strategy.Journal of molecular neuroscience : MN · 2024Article
- New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Review
- Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response.Cancer & metabolism · 2024Article
- Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.International journal of molecular sciences · 2023Review
- The development of a hiPSC-based platform to identify tissue-dependencies of IDH1 R132H.Cell death discovery · 2023Article
- Amino acid metabolism reprogramming: shedding new light on T cell anti-tumor immunity.Journal of experimental & clinical cancer research : CR · 2023Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply of macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy in cancer therapy. Several tumors excessively metabolize glutamine to generate precursors for nonessential amino acids, nucleotides, and lipids, in a process called glutaminolysis. Here we show that pharmacological inhibition of glutaminase (GLS) eradicates glioblastoma stem-like cells (GSCs), a small cell subpopulation in glioblastoma (GBM) responsible for therapy resistance and tumor recurrence. Treatment with small molecule inhibitors compound 968 and CB839 effectively diminished cell growth and in vitro clonogenicity of GSC neurosphere cultures. However, our pharmaco-metabolic studies revealed that only CB839 inhibited GLS enzymatic activity thereby limiting the influx of glutamine derivates into the TCA cycle. Nevertheless, the effects of both inhibitors were highly GLS specific, since treatment sensitivity markedly correlated with GLS protein expression. Strikingly, we found GLS overexpressed in in vitro GSC models as compared with neural stem cells (NSC). Moreover, our study demonstrates the usefulness of in vitro pharmaco-metabolomics to score target specificity of compounds thereby refining drug development and risk assessment.
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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.