Metformin, an Anti-diabetic Drug to Target Leukemia

Giulia Biondani, Jean-François Peyron

Metformin, a widely used anti-diabetic molecule, has attracted a strong interest in the last 10 years as a possible new anti-cancer molecule. Metformin acts by interfering with mitochondrial respiration, leading to an activation of the AMPK tumor-suppressive pathway to promote catabolic-energy saving reactions and block anabolic ones that are associated with abnormal cell proliferation. Metformin also acts at the organism level. In type 2 diabetes patients, metformin reduces hyperglycemia and increases insulin sensitivity by enhancing insulin-stimulated glucose uptake in muscles, liver, and adipose tissue and by reducing glucose output by the liver. Lowering insulin and insulin-like growth factor 1 (IGF-1) levels that stimulate cancer growth could be important features of metformin's mode of action. Despite continuous progress in treatments with the use of targeted therapies and now immunotherapies, acute leukemias are still of very poor prognosis for relapse patients, demonstrating an important need for new treatments deriving from the identification of their pathological supportive mechanisms. In the last decade, it has been realized that if cancer cells modify and reprogram their metabolism to feed their intense biochemical needs associated with their runaway proliferation, they develop metabolic addictions that could represent attractive targets for new therapeutic strategies that intend to starve and kill cancer cells. This Mini Review explores the anti-leukemic potential of metformin and its mode of action on leukemia metabolism.