title: Repurposing old drugs to chemoprevention: the case of metformin.
abstract: Multiple epidemiologic studies have documented an association between the anti-diabetic agent metformin and reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models or more recent epidemiological studies. The purpose of this paper is to examine metformin's chemopreventive potential by reviewing relevant mechanisms of action, preclinical evidence of efficacy, updated epidemiologic evidence after correction for potential biases and confounders, and recently completed and ongoing clinical trials. Although repurposing drugs with well described mechanisms of action and safety profiles is an appealing strategy for cancer prevention, there is no substitute for well executed late phase clinical trials to define efficacy and populations that are most likely to benefit from an intervention.
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Brandy M
authors.initials: BM
authors.lastname: Heckman-Stoddard
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gandini
authors.affiliation: Office of the Scientific Director, E.O. Ospedali Galliera, Genoa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Puntoni
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Dunn
authors.affiliation: Division of Medical Oncology, E.O. Ospedali Galliera, Genoa, Italy; Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: DeCensi
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA. Electronic address: szaboe@mail.nih.gov.
authors.forename: Eva
authors.initials: E
authors.lastname: Szabo
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018890:Chemoprevention; D003920:Diabetes Mellitus / Q000188:drug therapy; D058492:Drug Repositioning; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015994:Incidence; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D007004:Hypoglycemic Agents; D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Chemoprevention; Metformin; Repurposing