Repurposing old drugs to chemoprevention: the case of metformin

Semin Oncol. 2016 Feb;43(1):123-133. doi: 10.1053/j.seminoncol.2015.09.009. Epub 2015 Sep 8.

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.

Keywords: Chemoprevention; Metformin; Repurposing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Anticarcinogenic Agents / therapeutic use
  • Chemoprevention
  • Diabetes Mellitus / drug therapy
  • Drug Repositioning*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Incidence
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Neoplasms / epidemiology
  • Neoplasms / prevention & control*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Anticarcinogenic Agents
  • Hypoglycemic Agents
  • Metformin
  • MTOR protein, human
  • TOR Serine-Threonine Kinases