ArticleSignal transduction and targeted therapy
Central role of lactate and proton in cancer cell resistance to glucose deprivation and its clinical translation.
Article in Signal transduction and targeted therapy. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
What it found
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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
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Melatonin in glioblastoma therapy: clinical promise and mechanistic insights from bench to bedside.Neurosurgical review · 2026Pooled it
- Interplay Between Glucose Metabolism and Chromatin Modifications in Cancer.Frontiers in cell and developmental biology · 2021Pooled it
- A pathomics model for predicting lactate-related prognostic risk groups and their biological mechanisms in lung adenocarcinoma.Translational cancer research · 2026Article
- Lactate as a Master Regulator of Immune Suppression: From Metabolic Waste to Epigenetic Checkpoint in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Intratumoral bicarbonate functions as an adjuvant to potentiate PD-1 blockade in hepatocellular carcinoma.Oncogene · 2026Article
- Intracellular lactic acidosis reprograms glycolysis and mitochondrial anaplerosis in cancer cells.The Journal of biological chemistry · 2026Article
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Redox regulation of cell migration via Nischarin S-glutathionylation.Free radical biology & medicine · 2026Article
- Metal-based nanomaterials achieve tumor treatment strategies by overcoming the blood-brain barrier of glioma and responding to the tumor microenvironment.Materials today. Bio · 2026Review
- Review
- Targeting lactic acidosis in the tumor microenvironment: Enhancing TACE efficacy in hepatocellular carcinoma.Liver research (Beijing, China) · 2025Review
- Application value of a prognostic risk model based on lactate-related genes in non-small cell lung cancer.Translational cancer research · 2025Article
- Redox Regulation of Cell Migration via Nischarin S-glutathionylation.bioRxiv : the preprint server for biology · 2025Article
- Bicarbonate-integrated transarterial chemoembolization (TACE) in real-world hepatocellular carcinoma.Signal transduction and targeted therapy · 2025Article
- The integrated single-cell analysis interpret the lactate metabolism-driven immune suppression in triple-negative breast cancer.Discover oncology · 2025Article
- UDP-glucose regulates dendritic cell mitochondrial respiration via a nitric oxide-dependent mechanism.Journal of leukocyte biology · 2025Article
- Immunological profile of lactate metabolism-related genes in Psoriasis a comprehensive analysis based on bulk and single-cell RNA sequencing data.Scientific reports · 2025Article
- Protein phosphatase PP2Cα S-glutathionylation regulates cell migration.The Journal of biological chemistry · 2024Article
- Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.Nature communications · 2024Article
- Challenges of Spatially Resolved Metabolism in Cancer Research.Metabolites · 2024Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting common weaknesses of cancer is an important strategy for cancer therapy. Glucose is a nutrient that maintains essential cellular metabolism, supporting cancer cell survival, growth and proliferation. Depriving glucose rapidly kills cancer cells. Most cancer cells possess a feature called Warburg effect, which refers to that cancer cells even with ample oxygen exhibit an exceptionally high glycolysis rate and convert most incoming glucose to lactate. Although it is recognized that Warburg effect confers growth advantage to cancer cells when glucose supply is sufficient, this feature could be considered as a fatal weakness of cancer cells when glucose supply is a problem. As glucose supply in many solid tumors is poor, and as most cancer cells have exceptionally high glycolytic capacity, maximizing cancer cell glycolysis rate would possibly exhaust intratumoral glucose, leading cancer cell to death. Lactate and proton are two common factors in solid tumors, they jointly protect cancer cells against glucose deprivation, and they are also powerful regulators dictating glucose metabolic phenotypes of cancer cells. Disrupting the joint action of lactate and proton, for example, by means of bicarbonate infusion into tumor, could maximize cancer cell glycolytic rate to rapidly use up glucose, expose their vulnerability to glucose deprivation and ultimately kill cancer cells. A pilot clinical study demonstrated that this approach achieved a remarkable improvement in local control of large and huge hepatocellular carcinoma.
Identifiers
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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.