ArticleOncotarget2017
Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 135 citations in OpenAlex.
- Results of the Phase I/II Study and Preliminary B-cell Gene Signature of Combined Inhibition of Glutamine Metabolism and EGFR in Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Glutaminase inhibition in combination with azacytidine in myelodysplastic syndromes: a phase 1b/2 clinical trial and correlative analyses.Nature cancer · 2024Trial
- A metabolic trade-off between malignant plasma cells and mesenchymal stromal cells sustains multiple myeloma growth.Blood neoplasia · 2026Article
- Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming.Journal of advanced research · 2026Review
- PYCR1 inhibition in bone marrow stromal cells enhances bortezomib sensitivity in multiple myeloma cells by altering their metabolism.Molecular oncology · 2026Article
- Targeting the Glutaminolysis Pathway in Glaucoma-Associated Fibrosis.International journal of molecular sciences · 2025Review
- Cancer targeting carfilzomib nanomedicine: a comprehensive review of delivery vehicles and efficacy.Nanomedicine (London, England) · 2025Review
- A pancancer analysis reveals the oncogenic role of glutaminase 1 (GLS1) in tumor metabolism and immune evasion: a bioinformatics analysis.Discover oncology · 2025Article
- Carfilzomib resistance in multiple myeloma: A comparative metabolomic analysis.Journal of applied genetics · 2025Article
- TCA cycle-derived oncometabolites in cancer and the immune microenvironment.Journal of biomedical science · 2025Review
- Spatiotemporal Heterogeneity of Tumor Glucose Metabolism Reprogramming: From Single-Cell Mechanisms to Precision Interventions.International journal of molecular sciences · 2025Review
- Antiviral potential of diosmin against influenza A virus.Scientific reports · 2025Article
- The anti-diabetic PPARγ agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer.Molecular cancer · 2025Article
- A hormetic response model for glutamine stress in cancer.Trends in cancer · 2025Review
- Targeting Caveolin-1 in Multiple Myeloma Cells Enhances Chemotherapy and Natural Killer Cell-Mediated Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inhibition of glutaminase elicits senolysis in therapy-induced senescent melanoma cells.Cell death & disease · 2024Article
- Glutamine is critical for the maintenance of type 1 conventional dendritic cells in normal tissue and the tumor microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Pyruvate metabolism dictates fibroblast sensitivity to GLS1 inhibition during fibrogenesis.JCI insight · 2024Article
- Targeting Metabolic-Redox Nexus to Regulate Drug Resistance: From Mechanism to Tumor Therapy.Antioxidants (Basel, Switzerland) · 2024Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Curative responses in the treatment of multiple myeloma (MM) are limited by the emergence of therapeutic resistance. To address this problem, we set out to identify druggable mechanisms that convey resistance to proteasome inhibitors (PIs; e.g., bortezomib), which are cornerstone agents in the treatment of MM. In isogenic pairs of PI sensitive and resistant cells, we observed stark differences in cellular bioenergetics between the divergent phenotypes. PI resistant cells exhibited increased mitochondrial respiration driven by glutamine as the principle fuel source. To target glutamine-induced respiration in PI resistant cells, we utilized the glutaminase-1 inhibitor, CB-839. CB-839 inhibited mitochondrial respiration and was more cytotoxic in PI resistant cells as a single agent. Furthermore, we found that CB-839 synergistically enhanced the activity of multiple PIs with the most dramatic synergy being observed with carfilzomib (Crflz), which was confirmed in a panel of genetically diverse PI sensitive and resistant MM cells. Mechanistically, CB-839 enhanced Crflz-induced ER stress and apoptosis, characterized by a robust induction of ATF4 and CHOP and the activation of caspases. Our findings suggest that the acquisition of PI resistance involves adaptations in cellular bioenergetics, supporting the combination of CB-839 with Crflz for the treatment of refractory MM.
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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.