Metformin in cancer prevention and therapy

Abstract

The prevalence of diabetes is dramatically increasing worldwide. The results of numerous epidemiological studies indicate that diabetic population is not only at increased risk of cardiovascular complications, but also at substantially higher risk of many forms of malignancies. The use of metformin, the most commonly prescribed drug for type 2 diabetes, was repeatedly associated with the decreased risk of the occurrence of various types of cancers, especially of pancreas and colon and hepatocellular carcinoma. This observation was also confirmed by the results of numerous meta-analyses. There are however, several unanswered questions regarding the exact mechanism of the anticancer effect of metformin as well as its activity against various types of cancer both in diabetic and nondiabetic populations. In the present work we discuss the proposed mechanism(s) of anticancer effect of metformin and preclinical and clinical data suggesting its anticancer effect in different populations.

Keywords: Metformin; cancer; clinical evidence; molecular action.

Figure 1

Proposed molecular action of metformin in cancer cells. Abbreviations: Akt, protein kinase B; AMPK, AMP-activated protein kinase; Atg13, autophy-related protein 13; 4EBP1, eIF4E binding ptotein, eIF4E, eukaryotic translation initiation factor 4E; PI3K, phosphoinositide 3-kinase; p70S6K, ribosomal protein S6 kinase; Rag GTPase, Ras-related GTPase; REDD1, regulated in development and DNA damage responses 1; TSC2, tuberous sclerosis complex protein 2.