Observational studyJournal of the National Cancer Institute2024
Metformin boosts antitumor immunity and improves prognosis in upfront resected pancreatic cancer: an observational study.
Observational study in Journal of the National Cancer Institute, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis 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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Bibliometric analysis of metformin as an immunomodulator (2013-2024).Frontiers in immunology · 2024Pooled it
- p53 and p21 Status Influences Cellular Response to Metformin inCurrent issues in molecular biology · 2026Article
- A Phase 2 Feasibility Study Combining Pembrolizumab and Metformin in patients with Metastatic Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Metformin as a Multifaceted Therapeutic Agent for Gastrointestinal Diseases: Mechanisms, Clinical Efficacy, and Future Directions.Pharmacology research & perspectives · 2026Review
- Review
- Novel genetic insights into causal effects of potential metformin targets and immune mediation on sepsis.Biology direct · 2026Article
- Impact of diabetes mellitus on treatment efficacy in patients with advanced pancreatic cancer: the Italian, multicenter, observational PANCAKE study.ESMO gastrointestinal oncology · 2026Article
- Mitophagy in pancreatic cancer: mechanistic insights and implications for novel therapeutic strategies.Cell death discovery · 2026Review
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Neg-entropy is the true drug target for chronic diseases.Acta pharmaceutica Sinica. B · 2026Review
- Metformin reshapes the tumor microenvironment and enhances prognosis in invasive pancreatic ductal adenocarcinoma with diabetes mellitus.Journal of gastrointestinal oncology · 2025Article
- Unusual Manifestations of Primary Pancreatic Neoplasia.Cancers · 2025Review
- Unlocking Novel Therapeutic Potential of Angiotensin II Receptor Blockers.International journal of molecular sciences · 2025Review
- Mapping the current research landscape of metformin in cancer based on bibliometric analysis.Discover oncology · 2025Article
- Obesity and Pancreatic Diseases: From Inflammation to Oncogenesis and the Impact of Weight Loss Interventions.Nutrients · 2025Review
- Radio-chemotherapy and metformin selectively modulate the heterogeneous landscape of glioma with ribosome biogenesis, long non coding RNA and immune-escape markers as major player.International journal of biological sciences · 2025Article
- Ivosidenib enhances cisplatin sensitivity in ovarian cancer by reducing cancer cell stemness.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Drug functional remapping: a new promise for tumor immunotherapy.Frontiers in oncology · 2025Review
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- Extrinsic and Cell-Intrinsic Stress in the Immune Tumor Micro-Environment.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBeyond demographic and immune factors, metabolic considerations, particularly metformin's recognized impact in oncology, warrant exploration in treating pancreatic cancer. This study aimed to investigate the influence of metformin on patient survival and its potential correlation with distinct immune profiles in pancreatic ductal adenocarcinoma (PDAC) tumors.
methodsWe included 82 upfront resected and 66 gemcitabine-based neoadjuvant chemoradiotherapy (nCRT)-treated patients from the PREOPANC randomized controlled trial (RCT). Transcriptomic NanoString immunoprofiling was performed for a subset of 96 available resected specimens.
resultsDisparities in survival outcomes and immune profiles were apparent between metformin and non-metformin users in upfront resected patients but lacking in nCRT-treated patients. Compared to non-metformin users, upfront resected metformin users showed a higher median overall survival (OS) of 29 vs 14 months and a better 5-year OS rate of 19% vs 5%. Furthermore, metformin use was a favorable prognostic factor for OS in the upfront surgery group (HR = 0.56; 95% CI = 0.32 to 0.99). Transcriptomic data revealed that metformin users significantly underexpressed genes related to pro-tumoral immunity, including monocyte to M2 macrophage polarization and activation. Furthermore, the relative abundance of anti-inflammatory CD163+ MRC1+ M2 macrophages in non-metformin users and immune-activating CD1A+ CD1C+ dendritic cells in metformin users was heightened (P < .001).
conclusionThis study unveils immune profile changes resulting from metformin use in upfront resected pancreatic cancer patients, possibly contributing to prolonged survival outcomes. Specifically, metformin use may decrease the abundance and activity of pro-tumoral M2 macrophages and increase the recruitment and function of tumor-resolving DCs, favoring antitumor immunity.[PREOPANC trial EudraCT: 2012-003181-40].
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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 Socratic graph.