title: Expanding the therapeutic spectrum of metformin: from diabetes to cancer.
abstract: BACKGROUND
  Metformin, an oral hypoglycemic agent, was introduced in the clinical practice for the treatment of type 2 diabetes mellitus more than a half-century ago. Over the years, several studies demonstrated that diabetic patients treated with metformin have a lower incidence of cancer, raising the hypothesis that the spectrum of clinical applications of the drug could be expanded also to cancer therapy. Following these initial findings, a large number of studies were performed aimed at elucidating the effects of metformin on different types of tumor, at explaining its direct and indirect anti-cancer mechanisms and at identifying the molecular pathways targeted by the drug. Several clinical trials were also performed aimed at evaluating the potential anti-cancer effect of metformin among diabetic and non-diabetic patients affected by different types of cancer. While the results of several clinical studies are encouraging, a considerable number of other investigations do not support a role of metformin as an anti-cancer agent, and highlight variables possibly accounting for discrepancies.
  
  
  OBJECTIVE
  We hereby review the results of in vitro and in vivo studies addressing the issue of the anti-cancer effects of metformin.
  
  
  CONCLUSIONS
  If in vitro data appear solid, the results provided by in vivo studies are somehow controversial. In this view, larger studies are needed to fully elucidate the role of metformin on cancer development and progression, as well as the specific clinical settings in which metformin could become an anti-cancer drug.
authors.affiliation: Chair of Endocrinology, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Fondazione Salvatore Maugeri I.R.C.C.S., University of Pavia, Via Maugeri 10, 27100, Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Coperchini
authors.affiliation: Chair of Endocrinology, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Fondazione Salvatore Maugeri I.R.C.C.S., University of Pavia, Via Maugeri 10, 27100, Pavia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Leporati
authors.affiliation: Chair of Endocrinology, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Fondazione Salvatore Maugeri I.R.C.C.S., University of Pavia, Via Maugeri 10, 27100, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rotondi
authors.affiliation: Chair of Endocrinology, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Fondazione Salvatore Maugeri I.R.C.C.S., University of Pavia, Via Maugeri 10, 27100, Pavia, Italy. luca.chiovato@fsm.it.
authors.forename: L
authors.initials: L
authors.lastname: Chiovato
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Cancer; Diabetes; Metformin; Therapy