Final Report Summary - MYCNEXT (Connecting the activities of c-Myc in genome regulation, cellular growth control and oncogenesis)
Having mapped Myc-regulated genes in B-cell lymphomas, we carried out secondary genetic screens to determine which of these genes are critical for tumor maintenance. Among others, we unraveled a critical role for genes encoding mitochondrial ribosomal proteins. Inhibition of mitochondrial translation with the antibiotic Tigecycline was synthetic-lethal with Myc activation, impaired respiratory activity and tumor cell survival in vitro, and significantly extended life-span in lymphoma-bearing mice. We have thus identified a novel Myc-induced metabolic dependency that can be targeted by common antibiotics, opening new therapeutic perspectives in Myc-overexpressing tumors.