The beneficial effects of metformin on cancer prevention and therapy: a comprehensive review of recent advances

Pouya Saraei,1 Ilia Asadi,1 Muhammad Azam Kakar,2 Nasroallah Moradi-Kor1,31Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran; 2Director Planning and Development, L&DD Department, Quetta, Balochistan, Pakistan; 3Research Center of Physiology, Semnan University of Medical Sciences, Semnan, IranAbstract: Metformin is a widely used drug in today’s prescriptions by physicians due to its specific effects in treating and curing type II diabetes. Diabetes is a common disease that may occur throughout human life, and can increase the likelihood of the occurrence of various types of cancer, such as colon, rectum, pancreas and liver cancers, compared to non-diabetic patients. Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase(AMPK), and thus prevents protein synthesis and cell growth. Metformin can activate p53 by activatingAMPK and thereby ultimately stop the cell cycle. Given the potential of metformin in the treatment of cancer, it can be used in radiotherapy, chemotherapy and to improve the response to treatment inandrogen derivatives (ADT), and also, according to available evidence, metformin can also be used to prevent various types of cancers. Generally, metformin can: 1) reduce the incidence of cancers, 2) reduce the mortality from cancers, 3) increase the response to treatment in cancer cells when using radiotherapy and chemotherapy, 4) optimize tumor movement and reduce the malignancy, 5) reduce the likelihood of relapse, and 6) reduce the damaging effects of ADT. Therefore, this drug can be used as a complementary therapeutic agent for cancer treatment and prevention. In this review, we have summarized the data from various experimental and clinical studies and highlight the possible potential effects of metformin on cancer therapeutic responses.Keywords: metformin, AMPK pathway, mTOR pathway, LKB1, radiation, prevention and treatment of cancer