ArticleBiomolecules2021
Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin.
Article in Biomolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Bibliometric analysis of metformin as an immunomodulator (2013-2024).Frontiers in immunology · 2024Pooled it
- PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas.Current oncology (Toronto, Ont.) · 2022Pooled it
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.Experimental & molecular medicine · 2026Review
- Rewiring tumor metabolism: heterogeneity, oncometabolites, and adaptive plasticity.Experimental hematology & oncology · 2026Review
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
- Lactate and lactylation: metabolic architects of tumor progression and metastasis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- [Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- A Machine Learning-Guided Approach for Identifying Potential HCAR1 Antagonists in Lactate-Driven Cancers.ACS omega · 2026Article
- Metabolic rewiring of the tumor microenvironment: therapeutic intervention of multi-pathway adaptations to impede cancer metastasis.Frontiers in molecular biosciences · 2026Review
- Immunometabolic Reprogramming in Hepatocellular Carcinoma Mechanisms, Biomarkers, and Therapeutic Implications.Oncology research · 2026Review
- Metformin Sensitizes HR+/HER2- Breast Cancer Cells to CDK4/6 Inhibitor via Suppressing of PI3K/AKT/mTOR Signaling Pathway.Drug design, development and therapy · 2026Article
- Selegiline, a monoamine oxidase-B inhibitor as a modulator of metabolic reprogramming for cancer therapy: a review.Frontiers in pharmacology · 2026Review
- The multifaceted functions of lactate and its translational potentials in cancer.Frontiers in pharmacology · 2026Review
- Functional and Mechanistic Insights of 3-Hydroxybutyrate (3-OBA) in Bladder Cancer.Molecules (Basel, Switzerland) · 2025Article
- GPR81 nuclear transportation is critical for cancer growth: Interaction of lactate receptor signaling and cell-extracellular matrix mechanotransduction.World journal of clinical oncology · 2025Article
- Lactylation in cancer biology: Unlocking new avenues for research and therapy.Cancer communications (London, England) · 2025Review
- Lactate and lactylation in tumor immunity.Frontiers of medicine · 2025Review
- Influence of lactate in resistance to anti‑PD‑1/PD‑L1 therapy: Mechanisms and clinical applications (Review).Molecular medicine reports · 2025Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is a widely used antidiabetic drug for cancer prevention and treatment. However, the overproduction of lactic acid and its inefficiency in cancer therapy limit its application. Here, we demonstrate the synergistic effects of the lactate/GPR81 blockade (3-hydroxy-butyrate, 3-OBA) and metformin on inhibiting cancer cells growth in vitro. Simultaneously, this combination could inhibit glycolysis and OXPHOS metabolism, as well as inhibiting tumor growth and reducing serum lactate levels in tumor-bearing mice. Interestingly, we observed that this combination could enhance the functions of Jurkat cells in vitro and CD8
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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.