Preventive and therapeutic role of metformin. (1) Metformin use can prevent malignant transformation and tumorigenesis via systemic and direct effect. (2) Metformin can act as an adjuvant or neoadjuvant agent. In cancer cells without functional LKB1 and inactivation of AMPK, metformin induces metabolic catastrophe and apoptosis (cytotoxic), while in the presence of LKB1, metformin activates AMPK, leading to inhibition of mTOR and cell cycle arrest (cytostatic). (3) Metformin suppresses EMT/CSCs, which can prevent metastasis and reverse drug resistance.