Metastasis is an intricate process by which a small number of cancer cells from the primary tumor site undergo numerous alterations, which enables them to form secondary tumors at another and often multiple sites in the host. Transition of a cancer cell from epithelial to mesenchymal phenotype is thought to be the first step in the progression of metastasis. Recently, the recognition of cancer stem cells has added to the perplexity in understanding metastasis, as studies suggest cancer stem cells to be the originators of metastasis. All current and investigative drugs have been unable to prevent or reverse metastasis, as a result of which most metastatic cancers are incurable. A potential drug that can be considered is metformin, an oral hypoglycemic drug. In this review we discuss the potential of metformin in targeting both epithelial to mesenchymal transition and cancer stem cells in combating cancer metastases. 1. Introduction Metastasis is the process by which cancer cells translocate from their primary site to distant organs and establish secondary tumors. This simplified definition does not do justice to the complex enigmatic phenomenon that still lacks clear understanding. It is mainly because of metastasis that most cancers become incurable and result in death. It is these metastatic cells that escape the effects of chemotherapy and result in poor patient outcomes. Thus, a deeper knowledge of the process is crucial to devise therapeutic interventions that will result in better outcomes and survival for patients with metastatic disease. Until recently, the initiation of metastasis was solely attributed to the process of epithelial to mesenchymal (EMT) transition where a differentiated tumor cell transforms into a more aggressive, motile, and resistant cell. A cell after undergoing EMT was thought to be able to break the confines of its parent tumor and travel via lymphatic-blood system to a new receptive environment, where it would establish a new tumor. A full understanding of the EMT process is lacking. Recently, research efforts from a number of sources led to the identification of cancer stem cells (CSCs) [1, 2]. Some of the data generated suggest that these CSC may be at the origin of cancer metastasis [3–5]. All current and investigative drugs have been unable to prevent or reverse metastasis. A better understanding of the process is prerequisite to design successful drugs and strategies to manage the presently untreatable metastasis. One potential drug that can be considered for this aspect is metformin. Metformin is a well-established
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