ArticleTranslational oncology2020
Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer.
Article in Translational oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Glutamine prevents diarrhea in colorectal cancer patients undergoing chemotherapy or chemoradiotherapy: a meta-analysis.BMC gastroenterology · 2025Pooled it
- 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
- 70 Years of DON and Beyond: Glutaminase Inhibition as a Synergistic Strategy in Cancer Combination Therapy.Pharmaceutics · 2026Review
- Tumor Anti-Angiogenesis Therapy and Its Influence on Immune Cell Function in the Tumor Microenvironment.Cancer medicine · 2026Review
- Cdk5 regulates glutamine metabolism in colorectal cancer via the EZH2-GLS1 axis.Cancer & metabolism · 2025Article
- Glutaminase inhibitor CB-839 causes metabolic adjustments in colorectal cancer cells.Scientific reports · 2025Article
- Therapeutic Potential of Glutaminase Inhibition Targeting Metabolic Adaptations in Resistant Melanomas to Targeted Therapy.International journal of molecular sciences · 2025Article
- Subclonal response heterogeneity to define cancer organoid therapeutic sensitivity.Scientific reports · 2025Article
- Identification of an Amino Acid Metabolism Reprogramming Signature for Predicting Prognosis, Immunotherapy Efficacy, and Drug Candidates in Colon Cancer.Applied biochemistry and biotechnology · 2025Article
- Microbiota-host metabolism reprogramming in colorectal cancer: from pathogenesis to precision therapies.Frontiers in oncology · 2025Review
- Metabolic mechanisms of immunotherapy resistance.Exploration of targeted anti-tumor therapy · 2025Review
- Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment.Biomarker research · 2024Review
- Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy.Molecular cancer · 2024Review
- Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.Frontiers in pharmacology · 2024Review
- New plasma diagnostic markers for colorectal cancer: transporter fragments of glutamate tRNA origin.Journal of Cancer · 2024Article
- Participation of protein metabolism in cancer progression and its potential targeting for the management of cancer.Amino acids · 2023Review
- Negative correlation between acetyl-CoA acyltransferase 2 and cetuximab resistance in colorectal cancer.Acta biochimica et biophysica Sinica · 2023Article
- The Metabolism and Immune Environment in Diffuse Large B-Cell Lymphoma.Metabolites · 2023Review
- Animal Models and Their Role in Imaging-Assisted Co-Clinical Trials.Tomography (Ann Arbor, Mich.) · 2023Review
- Feasibility of [Tomography (Ann Arbor, Mich.) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Improving response to epidermal growth factor receptor (EGFR)-targeted therapies in patients with advanced wild-type (WT) RAS colorectal cancer (CRC) remains an unmet need. In this preclinical work, we evaluated a new therapeutic combination aimed at enhancing efficacy by targeting cancer cell metabolism in concert with EGFR. We hypothesized that combined blockade of glutamine metabolism and EGFR represents a promising treatment approach by targeting both the "fuel" and "signaling" components that these tumors need to survive. To explore this hypothesis, we combined CB-839, an inhibitor of glutaminase 1 (GLS1), the mitochondrial enzyme responsible for catalyzing conversion of glutamine to glutamate, with cetuximab, an EGFR-targeted monoclonal antibody in preclinical models of CRC. 2D and 3D in vitro assays were executed following treatment with either single agent or combination therapy. The combination of cetuximab with CB-839 resulted in reduced cell viability and demonstrated synergism in several cell lines. In vivo efficacy experiments were performed in cell-line xenograft models propagated in athymic nude mice. Tumor volumes were measured followed by immunohistochemical (IHC) analysis of proliferation (Ki67), mechanistic target of rapamycin (mTOR) signaling (pS6), and multiple mechanisms of cell death to annotate molecular determinants of response. In vivo, a significant reduction in tumor growth and reduced Ki67 and pS6 IHC staining were observed with combination therapy, which was accompanied by increased apoptosis and/or necrosis. The combination showed efficacy in cetuximab-sensitive as well as resistant models. In conclusion, this therapeutic combination represents a promising new precision medicine approach for patients with refractory metastatic WT RAS CRC.
Identifiers
What OpenQuestion holds
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.