Metformin as a New Anti-Cancer Drug in Pancreatic Cancer: Molecular Mechanisms and Clinical Implications

Background and aim: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-associated mortality worldwide with an overall five-year survival rate less than 7%. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin has recently gained attention as an anti-cancer drug and/or a chemoprevention agent because of its roles in inhibiting mTOR, lowering hyperinsulinemia, modulating inflammatory responses, and selectively killing cancer stem cells. Materials and Methods: To perform this research, we searched the English articles published in PubMed database applying the keywords of Pancreatic ductal adenocarcinoma; metformin; type II diabetes and Therapeutic Strategy.  Results: Metformin, an oral biguanide medication used to treat type-2 diabetes mellitus, has demonstrated potential therapeutic effect against PDAC. Many preclinical and clinical studies are currently evaluating metformin in combination with classical therapeutic agents as anti-cancer therapy. etformin has been shown to improve treatment outcomes in preclinical models of PDAC. In addition, it reduces the incidence of pancreatic cancer in diabetic patients as well as improves survival (reduced risk of death by 32%) in newly diagnosed cases . In vitro, metformin decreases cell survival and growth of pancreatic cancer cells and appears to target tumor-initiating cells. In vivo, metformin decreases growth of human pancreatic cancer cell lines xenografts in mice. However, the key underlying molecular mechanisms for the inhibitory effects of metformin on pancreatic cancer progression remain largely unknown.  Conclusion: Future research should prospectively evaluate metformin as a supplemental therapy in this population. A better understanding of the association between diabetes and pancreatic cancer (PC) may inform prevention and/or early detection strategies.

کلیدواژه ها:

Pancreatic ductal adenocarcinoma ، metformin ، type II diabetes ، Therapeutic Strategy