Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect

Metformin, as the preferred antihyperglycemic drug for type 2 diabetes, has been found to have a significant effect in inhibiting tumor growth in recent years. However, metformin alone in cancer treatment has the disadvantages of high dose concentrations and few targeted cancer types. Increasing studies have confirmed that metformin can be used in combination with conventional anticancer therapy to obtain more promising clinical benefits, which is expected to be rapidly transformed and applied in clinic. Some combination therapy strategies including metformin combined with chemotherapy, radiotherapy, targeted therapy and immunotherapy have been proven to have more significant antitumor effects and longer survival time than monotherapy. In this review, we summarize the synergistic antitumor effects and mechanisms of metformin in combination with other current conventional anticancer therapies. In addition, we update the research progress and the latest prospect of the metformin-combined application in the cancer treatment. This work could provide more evidence and future direction for the clinical application of metformin in antitumor.