Metformin—A Type 2 Diabetes Mellitus Drug—And Ovarian Cancer: Anticancer Mechanisms and Therapeutic Implications

Ovarian cancer is a devastating disease that is often diagnosed in the late stages. The typical therapeutic approach includes surgery plus cytotoxic drugs such as carboplatin and paclitaxel. In recent years, the advent of poly ADP-ribose polymerase (PARP) inhibitors such as olaparib has offered additional treatment opportunities for patients with BRCA mutations or homologous recombination deficiencies. Nevertheless, resistance to therapy usually occurs, leading to poor overall survival. Therefore, novel treatments are needed for this disease. One of the obstacles to successful treatment is the highly immunosuppressive nature of the ovarian cancer microenvironment. Recent strategies for the treatment of ovarian cancer and other types of cancer involve targeting the metabolism of cancer cells and other cells of the tumor microenvironment. One drug that has been investigated both in preclinical studies and clinical trials as an antitumor agent is metformin. This drug, typically used for the treatment of type-2 diabetes for its capability to lower blood glucose, can directly affect cancer cell growth and survival by activating the AMPK (adenosine monophosphate-activated protein kinase) pathway. Furthermore, it can affect the phenotype of other cells of the tumor microenvironment such as macrophages and T cells. In this review, we summarize the main characteristics of ovarian cancer and describe preclinical studies and clinical trials involving metformin as a therapeutic agent for this disease.