ArticleNature communications2019
Targeting glutamine-addiction and overcoming CDK4/6 inhibitor resistance in human esophageal squamous cell carcinoma.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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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.
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Who cites it
70 citing papers in PubMed, 103 citations in OpenAlex.
- Glutamine transporter SLC1A5 inhibits autophagy-mediated CD276 degradation to promote esophageal cancer progression.Cancer biology & therapy · 2026Article
- Review
- mTOR-driven autophagy suppression defines metabolic vulnerability in CDK4/6 inhibitor-resistant HRCell death & disease · 2026Article
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- Review
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- MYO1B in human disease: an actin-based motor linking membrane trafficking to oncogenic signaling, metastasis, and vascular aging.Frontiers in oncology · 2026Review
- Metformin sensitizes non-small cell lung cancer to CDK4/6 inhibitor treatment by reducing lysosomal trapping.Science China. Life sciences · 2026Article
- Improving Immune Checkpoint Therapy in the Tumor Microenvironment by Targeting T Cell Metabolism.Endocrine, metabolic & immune disorders drug targets · 2026Review
- The Mechanism ofCombinatorial chemistry & high throughput screening · 2026Article
- Targeting the Glutaminolysis Pathway in Glaucoma-Associated Fibrosis.International journal of molecular sciences · 2025Review
- Serum multiomics prediction of prognosis and adverse reactions to concurrent chemoradiotherapy in patients with esophageal cancer.British journal of cancer · 2025Article
- SLC6A14-mediated glutamine promotes SYTL4-CXCL8 axis activation to drive gemcitabine resistance and immune evasion in pancreatic cancer.Experimental & molecular medicine · 2025Article
- Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells.Oncogene · 2025Article
- Therapeutic Potential of Glutaminase Inhibition Targeting Metabolic Adaptations in Resistant Melanomas to Targeted Therapy.International journal of molecular sciences · 2025Article
- Review
- Risk of serum circulating environmental chemical residues to esophageal squamous cell carcinoma: a nested case-control metabolome-wide association study.Analytical and bioanalytical chemistry · 2025Article
- Squamous cell cancers of the aero-upper digestive tract: A unified perspective on biology, genetics, and therapy.Cancer cell · 2025Review
- Exploring metabolic reprogramming in esophageal cancer: the role of key enzymes in glucose, amino acid, and nucleotide pathways and targeted therapies.Cancer gene therapy · 2025Review
- Aging-associated mechanisms and metabolic vulnerabilities in esophageal carcinoma: an integrative review.Frontiers in cell and developmental biology · 2025Review
10 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
11 authors at 3 institutions in 1 country.
Funding
Abstract
The dysregulation of Fbxo4-cyclin D1 axis occurs at high frequency in esophageal squamous cell carcinoma (ESCC), where it promotes ESCC development and progression. However, defining a therapeutic vulnerability that results from this dysregulation has remained elusive. Here we demonstrate that Rb and mTORC1 contribute to Gln-addiction upon the dysregulation of the Fbxo4-cyclin D1 axis, which leads to the reprogramming of cellular metabolism. This reprogramming is characterized by reduced energy production and increased sensitivity of ESCC cells to combined treatment with CB-839 (glutaminase 1 inhibitor) plus metformin/phenformin. Of additional importance, this combined treatment has potent efficacy in ESCC cells with acquired resistance to CDK4/6 inhibitors in vitro and in xenograft tumors. Our findings reveal a molecular basis for cancer therapy through targeting glutaminolysis and mitochondrial respiration in ESCC with dysregulated Fbxo4-cyclin D1 axis as well as cancers resistant to CDK4/6 inhibitors.
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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.