Repurposing of Metformin as a Multifaceted and Multitasking Preventative and Treatment for Cancer

Abstract

Metformin is a cornerstone treatment of diabetes mellitus. Since 2005 when it has been first reported to reduce the risk of cancer in diabetics, a large number of preclinical and clinical studies have implicated its potential role as a preventative and adjunct therapy for a broad range of cancers. Whereas preclinical studies demonstrate its actions on a multitude of molecular pathways involving nearly all aspects of cancer development including metabolism, angiogenesis, apoptosis, autophagy, immunity, epigenetics, inflammation and crosstalk with the microbi-ome, other studies demonstrate its synergism with a range of anticancer modalities including chemotherapy, radiotherapy, immunotherapy, and targeted therapies. Furthermore, an increasing number of clinical studies not only confirm its preventative properties against cancers but have extended its potential for a possible adjunctive role in the neoadjuvant, adjuvant, maintenance and salvage therapies of cancer. This article intends to summarize the basic science that allows us to understand the complex multiple mechanisms of action of this remarkable multitasking molecule as well as review the recent meta-analyses that have summarized the clinical studies assessing the therapeutic efficacy of metformin for various cancers.