Metformin Targets Central Carbon Metabolism and Reveals Mitochondrial Requirements in Human Cancers.

ABSTRACT: Repurposing metformin for cancer therapy is attractive due to its safety profile, epidemiological evidence, and encouraging data from human clinical trials. Although it is known to systemically affect glucose metabolism in liver, muscle, gut, and other tissues, the molecular determinants that predict a patient response in cancer remain unknown. Here, we carry out an integrative metabolomics analysis of metformin action in ovarian cancer. Metformin accumulated in patient biopsies, and pathways involving nucleotide metabolism, redox, and energy status, all related to mitochondrial metabolism, were affected in treated tumors. Strikingly, a metabolic signature obtained from a patient with an exceptional clinical outcome mirrored that of a responsive animal tumor. Mechanistically, we demonstrat

SUBMITTER: Liu X 

PROVIDER: S-EPMC5889952 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature