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Metformin: review of epidemiology and mechanisms of action in pancreatic cancer

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Abstract

Pancreatic ductal adenocarcinoma continues to be a lethal disease, for which efficient treatment options are very limited. Increasing efforts have been taken to understand how to prevent or intercept this disease at an early stage. There is convincing evidence from epidemiologic and preclinical studies that the antidiabetic drug metformin possesses beneficial effects in pancreatic cancer, including reducing the risk of developing the disease and improving survival in patients with early-stage disease. This review will summarize the current literature about the epidemiological data on metformin and pancreatic cancer as well as describe the preclinical evidence illustrating the anticancer effects of metformin in pancreatic cancer. Underlying mechanisms and targets of metformin will also be discussed. These include direct effects on transformed pancreatic epithelial cells and indirect, systemic effects on extra-pancreatic tissues.

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Funding

Guido Eibl is supported by the National Institutes of Health, National Cancer Institute (P01CA236585), and the Hirshberg Foundation for Pancreatic Cancer Research. Enrique Rozengurt is supported by the National Institutes of Health, National Cancer Institute (P01CA236585), National Institute of Allergy and Infectious Diseases (R21AI156592), the Veterans Administration (I01BX003801), and the Hirshberg Foundation for Pancreatic Cancer Research.

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  1. Department of Surgery, David Geffen School of Medicine At UCLA, Los Angeles, CA, USA

    Guido Eibl

  2. Department of Medicine, David Geffen School of Medicine At UCLA, Los Angeles, CA, USA

    Enrique Rozengurt

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  1. Guido Eibl
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Correspondence to Guido Eibl.

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Eibl, G., Rozengurt, E. Metformin: review of epidemiology and mechanisms of action in pancreatic cancer. Cancer Metastasis Rev 40, 865–878 (2021). https://doi.org/10.1007/s10555-021-09977-z

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