title: Is it time to test biguanide metformin in the treatment of melanoma?
abstract: Metformin is the most widely used antidiabetic drug that belongs to the biguanide class. It is very well tolerated and has the major clinical advantage of not inducing hypoglycemia. Metformin decreases hepatic glucose production via a mechanism requiring liver kinase B1, which controls the metabolic checkpoint, AMP-activated protein kinase-mammalian target of rapamycin and neoglucogenic genes. The effects of metformin on this pathway results in reduced protein synthesis and cell proliferation. These observations have given the impetus for many investigations on the role of metformin in the regulation of tumor cell proliferation, cell-cycle regulation, apoptosis, and autophagy. Encouraging results from these studies have shown that metformin could potentially be used as an efficient anticancer drug in various neoplasms such as prostate, breast, lung, pancreas cancers, and melanoma. These findings are strengthened by retrospective epidemiological studies that have found a decrease in cancer risk in diabetic patients treated with metformin. In this review, we have focused our discussion on recent molecular mechanisms of metformin that have been described in various solid tumors in general and in melanoma in particular.
authors.affiliation: INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des Cellules Mélanocytaire: de la Pigmentation Cutanée au Mélanome, Nice, France; Université de Nice Sophia Antipolis, UFR de Médecine, Nice, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Cerezo
authors.forename: Tijana
authors.initials: T
authors.lastname: Tomic
authors.forename: Robert
authors.initials: R
authors.lastname: Ballotti
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rocchi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D008687:Metformin
keywords: AMP-activated protein kinase; apoptosis; cancers; melanoma; metformin