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Targeting metabolism for cancer treatment and prevention: metformin, an old drug with multi-faceted effects

Oncogene volume 32, pages 1475–1487 (2013)Cite this article

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Abstract

Understanding the complexity of cancer and of the underlying regulatory networks provides a new paradigm that tackles cancer development and treatment through a system biology approach, contemporarily acting on various intersecting pathways. Cancer cell metabolism is an old pathogenetic issue that has recently gained new interest as target for therapeutic approaches. More than 70 years ago, Warburg discovered that malignant cells generally have altered metabolism with high rates of glucose uptake and increased glycolysis, even under aerobic condition. Observational studies have provided evidence that impaired metabolism, obesity, hyperglycemia and hyperinsulinemia may have a role in cancer development, progression and prognosis, and actually diabetic and obese patients have increased cancer risk. On the other hand, caloric restriction has been shown to prolong life span and reduce cancer incidence in several animal models, having an impact on different metabolic pathways. Metformin, an antidiabetic drug widely used for over 40 years, mimics caloric restriction acting on cell metabolism at multiple levels, reducing all energy-consuming processes in the cells, including cell proliferation. By overviewing molecular mechanisms of action, epidemiological evidences, experimental data in tumor models and early clinical study results, this review provides information supporting the promising use of metformin in cancer prevention and treatment.

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Acknowledgements

This work was supported by the Ministero dell′Università e della Ricerca with the MIUR 5 × 1000 grant no. DO11/002 and by the Associazione Italiana per la Ricerca sul Cancro (AIRC grant no. R10/029). MAP would like to thank Dr Mathias Christian Zohoungbogbo who first introduced him to metformin. The authors wish to thank Dr Daniela Majerna for editorial assistance.

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Authors and Affiliations

  1. Scientific Directorate, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy

    M A Pierotti & C Melani

  2. Department of Predictive and Preventive Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy

    F Berrino & P Pasanisi

  3. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    M Gariboldi & A Mogavero

  4. Molecular Genetics of Cancer, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy

    M Gariboldi & A Mogavero

  5. Department of Pathology, Laboratory of Molecular Pathology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy

    T Negri & S Pilotti

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  1. M A Pierotti
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Pierotti, M., Berrino, F., Gariboldi, M. et al. Targeting metabolism for cancer treatment and prevention: metformin, an old drug with multi-faceted effects. Oncogene 32, 1475–1487 (2013). https://doi.org/10.1038/onc.2012.181

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