Metformin – the newer role of the old medicine - in cancer prevention and treatment!
Dr. Asish Kumar Biswas, Dr. Matin Ahmad Khan, Dr. Md Shadab Alam and Dr. AK Choudhary
The potential use of metformin as a novel cancer prevention strategy has generated much excitement in view of its low cost, favourable safety profile, and its potential for biological specificity in disrupting the association between obesity and cancer. Metformin, a biguanide derivative, is currently the ﬁrst-line drug for the treatment of type 2 diabetes (T2D) due to its ability to inhibit hepatic gluconeogenesis and trigger glucose uptake in skeletal muscle. Diﬀerent from other biguanides, metformin is a relatively safe and well-tolerated drug, with acknowledged pharmacokinetics and manageable toxicities. Besides glucose-lowering eﬀect, there is increasing interest in its anticancer potential. A huge amount of epidemiologic evidence shows that metformin exposure may reduce cancer incidence and improve cancer patients’ prognosis. Accumu- lating preclinical and clinical studies also demonstrate that metformin may not only exert anticancer properties in a spectrum of established malignancies but also have eﬀects in preventing tumor initiation. The mechanisms involved in the antineoplastic eﬀects of metformin are mainly divided into two categories: “indirect eﬀect” resulting from systemic changes in glucose or insulin levels and “direct eﬀect”on tumor cells The direct anticancer eﬀects of metformin are mainly explained by activation of adenosine monophosphate-activated protein kinase (AMPK) and a reduction in mammalian target of rapamycin (mTOR) signaling, which inhibits protein synthesis and gluconeogenesis. However, metformin may also exert antineoplastic properties in an AMPK- The prevalence of diabetes is dramatically increasing worldwide reaching epidemic proportion. Landmark of diabetes, chronic hyperglycemia leads to the development and progression of life-treating complications, predominantly cardiovascular. The results of several studies indicate that people with diabetes (mainly type 2, T2DM) are also at substantially higher risk of cancer of the pancreas, liver, endometrium, breast, colon, rectum and urinary bladder compared to individuals without this chronic disease However, the incidence of other types of cancer (e.g., lung, kidney, non-Hodgkin lymphomas) does not seem to be strongly associated with diabetes or the evidence is inconclusive Interestingly enough, it has been suggested that diabetes is associated with a lower risk for prostate cancer According to the American Diabetes Association and the American Cancer Society consensus report the relative risks imparted by diabetes are greatest (about two fold or higher) for cancers of the liver, pancreas, and endometrium, and lesser (about 1.2-1.5 fold) for cancers of the colon and rectum, breast, and bladder Clinical observations indicate that the prevalence of diabetes in newly diagnosed cancer patients ranges from 8% to 18%, suggesting bidirectional association between these two disease The association of diabetes and cancer was first reported as an incidental finding in 1932 Nowadays, this coexistence is well recognized, however in spite of the intensive studies its mechanism still remains unclear. There is a general agreement that T2DM and cancer share several common potential risk factors (e.g., aging, sex, obesity, physical inactivity, diet, alcohol, and smoking). In T2DM, insulin resistance and hyperinsulinemia (either endogenous due to insulin resistance or induced by administration of exogenous insulin formulations) are considered to be independent risk factors for cancer development In addition, hyperglycemia-related oxidative stress, accumulation of advances glycation end products as well as low-grade inflammation may also enhance the risk of malignant transformation Recent publications have also suggested the link between hypoglycemic medications and cancer The results of numerous preclinical, epidemiological and clinical studies suggested that metformin use is associated with inhibition of cancer cell growth and proliferation and reduction in all-cancer incidents in comparison with users of other hypoglycemic drugs. In the present work we discuss the proposed mechanism(s) of anticancer effect of metformin as well as preclinical and clinical data suggesting this beneficial effect. We describe the role of metformin in the prevention and treatment of a variety of cancers and summarize the molecular mechanisms that are currently well documented in the ability of metformin as an anticancer agent.
How to cite this article:
Dr. Asish Kumar Biswas, Dr. Matin Ahmad Khan, Dr. Md Shadab Alam, Dr. AK Choudhary. Metformin – the newer role of the old medicine - in cancer prevention and treatment!. Pharma Innovation 2017;6(6):130-134.