Mouse Models to Study Metformin Effects in Carcinogenesis

Abstract

Emerging evidence suggests that common drugs that were originally developed for other chronic conditions may also trigger protective actions against cancer development and progression. Early retrospective observational studies in diabetic patients indicated that among the most commonly used oral antihyperglycemic agents, the biguanide compound metformin was associated with a reduced risk of cancer or improved cancer prognosis. Indeed, numerous studies have been conducted in the last decade to investigate whether metformin could be repurposed as an antineoplastic agent. This chapter will discuss promising data gained through the use of mouse models to study the effects of metformin in carcinogenesis. Overall, metformin has consistently demonstrated encouraging antineoplastic activity in preclinical mouse models. While in certain types of cancer these responses are highly influenced by the systemic metabolic status of the host, in others it is more dependent on the cellular and molecular background of the primary tumor. What still remains a critical challenge is extrapolating these findings to the biological and behavioral complexities of neoplastic disease in humans. The positive findings obtained with a drug that is relatively affordable and safe as metformin in experimental mouse models of cancer should continue to guide the design and implementation of clinical trials. These studies should serve to validate and optimize the potential use of metformin in cancer chemoprevention and treatment, and ultimately impact the selection of the most suitable patients who can benefit from metformin in the oncologic setting.