ArticleOncotarget2016
Inhibition of mitochondrial glutaminase activity reverses acquired erlotinib resistance in non-small cell lung cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 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
- Structural reassignment of compound 968, an allosteric glutaminase inhibitor.Beilstein journal of organic chemistry · 2026Article
- The Emerging Roles of Metabolic Reprogramming in Non-Small Cell Lung Cancer Progression.Frontiers in bioscience (Landmark edition) · 2025Review
- The role of mitochondria in tumor metastasis and advances in mitochondria-targeted cancer therapy.Cancer metastasis reviews · 2024Review
- The significant role of amino acid metabolic reprogramming in cancer.Cell communication and signaling : CCS · 2024Review
- Metabolic Rewiring in Cancer: Small Molecule Inhibitors in Colorectal Cancer Therapy.Molecules (Basel, Switzerland) · 2024Review
- Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.Frontiers in pharmacology · 2024Review
- Role and therapeutic targeting of glutamine metabolism in non‑small cell lung cancer (Review).Oncology letters · 2023Review
- Therapeutic Targeting of Glutaminolysis as a Novel Strategy to Combat Cancer Stem Cells.International journal of molecular sciences · 2022Review
- Review
- Dysregulated Metabolism in EGFR-TKI Drug Resistant Non-Small-Cell Lung Cancer: A Systematic Review.Metabolites · 2022Review
- Targeting mitochondrial metabolism for precision medicine in cancer.Cell death and differentiation · 2022Review
- Targeting Energy Metabolism in Cancer Treatment.International journal of molecular sciences · 2022Review
- Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells.Journal of pharmaceutical analysis · 2021Article
- Role of metabolic reprogramming in drug resistance to epidermal growth factor tyrosine kinase inhibitors in non-small cell lung cancer.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- PolG Inhibits Gastric Cancer Glycolysis and Viability by Suppressing PKM2 Phosphorylation.Cancer management and research · 2021Article
- Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer.Translational oncology · 2020Article
- Review
- A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity.Cell death discovery · 2020Article
- Metabolic Plasticity in Chemotherapy Resistance.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib has been approved based on the clinical benefit in non-small cell lung cancer (NSCLC) patients over the past decade. Unfortunately, cancer cells become resistant to this agent via various mechanisms, and this limits the improvement in patient outcomes. Thus, it is urgent to develop novel agents to overcome erlotinib resistance. Here, we propose a novel strategy to overcome acquired erlotinib resistance in NSCLC by inhibiting glutaminase activity. Compound 968, an inhibitor of the glutaminase C (GAC), when combined with erlotinib potently inhibited the cell proliferation of erlotinib-resistant NSCLC cells HCC827ER and NCI-H1975. The combination of compound 968 and erlotinib not only decreased GAC and EGFR protein expression but also inhibited GAC activity in HCC827ER cells. The growth of erlotinib-resistant cells was glutamine-dependent as proved by GAC gene knocked down and rescue experiment. More importantly, compound 968 combined with erlotinib down-regulated the glutamine and glycolysis metabolism in erlotinib-resistant cells. Taken together, our study provides a valuable approach to overcome acquired erlotinib resistance by blocking glutamine metabolism and suggests that combination of EGFR-TKI and GAC inhibitor maybe a potential treatment strategy for acquired erlotinib-resistant NSCLC.
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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.