ArticlePloS one2021
The glutaminase inhibitor telaglenastat enhances the antitumor activity of signal transduction inhibitors everolimus and cabozantinib in models of renal cell carcinoma.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 47 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
- Telaglenastat plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase II ENTRATA Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Research progress in metabolic reprogramming and targeting metabolic pathways for clear cell renal cell carcinoma.Genes & diseases · 2026Review
- Metabolic reprogramming-mediated therapeutic resistance in renal cell carcinoma: Mechanisms and targeted intervention strategies.iScience · 2026Review
- 70 Years of DON and Beyond: Glutaminase Inhibition as a Synergistic Strategy in Cancer Combination Therapy.Pharmaceutics · 2026Review
- The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.Translational lung cancer research · 2026Review
- A ketogenic diet sensitizes pancreatic cancer to glutamine metabolism inhibitors.Cell reports. Medicine · 2026Article
- Systematic and precise interventions for KRAS-mutant cancers.Experimental hematology & oncology · 2026Review
- Cabozantinib After Immunotherapy in Advanced Renal Cell Carcinoma. The CARE Study by the Hellenic Gu Cancer Group.Cancer management and research · 2026Article
- Stroma-driven horizontal transfer of TCA-related proteins mediates metabolic plasticity and imatinib resistance in chronic myeloid leukemia.Cell communication and signaling : CCS · 2025Article
- Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review).International journal of oncology · 2025Review
- Article
- Metabolites as agents and targets for cancer immunotherapy.Nature reviews. Drug discovery · 2025Review
- Rational Design of Non-Toxic Multidrug Combinations Demonstrates Durable and Hypoxia-Enhanced Efficacy Against Renal Cell Carcinoma.Pharmaceutics · 2025Article
- Emerging roles of metabolic biomarkers in renal cell carcinoma: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2025Review
- Second-Line Systemic Therapies in Metastatic Renal Cell Carcinoma: Current Insights and Future Directions.Journal of cancer immunology · 2025Article
- MtDNA copy number enrichment is associated with poor prognosis and eosinophilic morphology in clear cell renal cell carcinoma.Pathology oncology research : POR · 2025Article
- Overexpression of BNIP3 in renal carcinoma cells can promote apoptosis of renal carcinoma cells through HIF-1α-BNIP3-mediated autophagy.Frontiers in oncology · 2025Article
- Knowledge-Based Therapeutics for Tricarboxylic Acid (TCA) Cycle-Deficient Cancers.Cold Spring Harbor perspectives in medicine · 2024Review
- Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.Seminars in immunopathology · 2024Review
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulated metabolism is a hallmark of cancer that manifests through alterations in bioenergetic and biosynthetic pathways to enable tumor cell proliferation and survival. Tumor cells exhibit high rates of glycolysis, a phenomenon known as the Warburg effect, and an increase in glutamine consumption to support the tricarboxylic acid (TCA) cycle. Renal cell carcinoma (RCC) tumors express high levels of glutaminase (GLS), the enzyme required for the first step in metabolic conversion of glutamine to glutamate and the entry of glutamine into the TCA cycle. We found that RCC cells are highly dependent on glutamine for proliferation, and this dependence strongly correlated with sensitivity to telaglenstat (CB-839), an investigational, first-in-class, selective, orally bioavailable GLS inhibitor. Metabolic profiling of RCC cell lines treated with telaglenastat revealed a decrease in glutamine consumption, which was concomitant with a decrease in the production of glutamate and other glutamine-derived metabolites, consistent with GLS inhibition. Treatment of RCC cells with signal transduction inhibitors everolimus (mTOR inhibitor) or cabozantinib (VEGFR/MET/AXL inhibitor) in combination with telaglenastat resulted in decreased consumption of both glucose and glutamine and synergistic anti-proliferative effects. Treatment of mice bearing Caki-1 RCC xenograft tumors with cabozantinib plus telaglenastat resulted in reduced tumor growth compared to either agent alone. Enhanced anti-tumor activity was also observed with the combination of everolimus plus telaglenastat. Collectively, our results demonstrate potent, synergistic, anti-tumor activity of telaglenastat plus signal transduction inhibitors cabozantinib or everolimus via a mechanism involving dual inhibition of glucose and glutamine consumption.
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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.