Metformin: a metabolic disruptor and anti-diabetic drug to target human leukemia.
There is a global and urgent need for expanding our current therapeutical arsenal against leukemia in order to improve their actual cure rates and fight relapse. Targeting the reprogrammed, altered cancer metabolism is an emerging strategy which should profoundly affect cancer cells in their intimate and irrepressible needs and addictions for nutrients uptake and incorporation into the biomass during malignant proliferation. We present here how metformin, an anti-diabetic drug that has attracted a strong interest for its recently discovered anti-cancer properties, can be envisioned as a new adjuvant approach to treat leukemia. Metformin may have a double-edged sword effect (i) by acting on the organism to decrease hyperglycaemia and hyperinsulinemia in diabetic patients and (ii) at the cellular level, by inhibiting the mTORC1-cancer supporting pathway through AMPK-dependent and independent mechanisms.
INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4: Inflammation, Cancer, Cancer Stem Cells, Nice F-06204, France; Université de Nice Sophia-Antipolis, Faculté de Médecine, Nice F-06107, France.
Célia
C
Rosilio
Harvard School of Public Health, Department of Genetics and Complex Diseases, Boston, MA 02115, USA.
Issam
I
Ben-Sahra
INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 7: Cellular and Molecular Physiopathology of Obesity and Diabetes, Nice F-06204, France; Université de Nice Sophia-Antipolis, Faculté de Médecine, Nice F-06107, France.
Frédéric
F
Bost
INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4: Inflammation, Cancer, Cancer Stem Cells, Nice F-06204, France; Université de Nice Sophia-Antipolis, Faculté de Médecine, Nice F-06107, France; Centre Hospitalier Universitaire de Nice, Service d'Oncologie Pédiatrique, Hôpital de l'Archet, Nice, France. Electronic address: peyron@unice.fr.
Jean-François
JF
Peyron
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007938:Leukemia / Q000188:drug therapy*; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D008687:Metformin
AMPK; Acute leukemia; Adjuvant chemotherapy; Metformin; mTOR