ArticleCancer immunology, immunotherapy : CII2021
Overcoming acquired resistance to PD-1 inhibitor with the addition of metformin in small cell lung cancer (SCLC).
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Immune checkpoints and immunoregulation in metabolic diseases and cancers: pathological mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2026Review
- Complete Response to Tislelizumab in an Elderly Patient With Metastatic Pulmonary Squamous Cell Carcinoma: Potential Synergy With Metformin and Multidisciplinary Management.Clinical case reports · 2026Article
- Metformin inhibits the growth of SCLC cells by inducing autophagy and apoptosis via the suppression of EGFR and AKT signalling.Scientific reports · 2025Article
- Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.The Journal of experimental medicine · 2025Article
- Living hybrid material based on probiotic with photothermal properties inhibits PD-L1 expression after tumouricidal photothermal therapy.Biomaterials translational · 2025Article
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- Mesoporous manganese nanocarrier target delivery metformin for the co-activation STING pathway to overcome immunotherapy resistance.iScience · 2024Article
- Research Progress on the Use of Metformin in Leukemia Treatment.Current treatment options in oncology · 2024Review
- The Metformin Immunoregulatory Actions in Tumor Suppression and Normal Tissues Protection.Current medicinal chemistry · 2024Review
- Prognostic impact of metformin in solid cancer patients receiving immune checkpoint inhibitors: novel evidences from a multicenter retrospective study.Frontiers in pharmacology · 2024Article
- Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment.Translational oncology · 2023Article
- Review
- PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment.Frontiers in immunology · 2023Review
- Low glucose availability potentiates the effects of metformin on model T cell activation and exhaustion markersFrontiers in endocrinology · 2023Article
- Research progress on the therapeutic effect and mechanism of metformin for lung cancer (Review).Oncology reports · 2023Review
- Addition of metformin for non-small cell lung cancer patients receiving antineoplastic agents.Frontiers in pharmacology · 2023Article
- A signature of six-hypoxia-related genes to evaluate the tumor immune microenvironment and predict prognosis in gastric cancer.BMC medical genomics · 2022Article
- Imaging Memory T-Cells Stratifies Response to Adjuvant Metformin Combined with αPD-1 Therapy.International journal of molecular sciences · 2022Article
- Targeting of the tumor immune microenvironment by metformin.Journal of cell communication and signaling · 2022Review
- Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin has been widely used as the treatment of type II diabetes mellitus for its anti-hyperglycemic effect. In recent years, it has also been extensively studied for its anti-cancer effect as it diminishes immune exhaustion of CD8 + tumor-infiltrating lymphocytes (TILs). It decreases apoptosis of CD8 + TILs, thereby enhancing T cell-mediated immune response to tumor cells. Here, we present a unique case of a patient with small cell lung cancer (SCLC) who exhibited an overall partial response as per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) since starting metformin in combination with nivolumab therapy. Our patient had been treated with nivolumab monotherapy for 2 years until she had progression of disease. After she was started on metformin along with nivolumab therapy, she has shown a significant durable response for over 6 months. Many patients develop resistance to immunotherapy such as antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Tumor hypoxia is one of the resistance factors. Signals activated by hypoxic environments in tumors are associated with decreased sensitivity to the PD-1 blockade. Metformin inhibits oxygen consumption in tumor cells in vitro and in vivo, reducing intratumoral hypoxia. These data suggest that metformin can improve susceptibility to anti-PD-1 treatment. To the best of our knowledge, our case is the first reported example demonstrating a proof-of-concept that metformin can contribute to overcoming acquired resistance to PD-1 inhibitors.
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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.