Role of Oncogenes and Tumor Suppressors in Metabolic Reprogramming and Cancer Therapeutics: A Review

Abstract

Recently there has been a renewed interest on the signaling pathways and metabolic changes in cancer cells. It is well known that there are several oncogenes and tumor suppressors that affect cancer metabolism and re-engineer it for better growth and survival. The best description of tumor metabolism is the Warburg effect, which shifts from ATP production through oxidative phosphorylation to ATP production through glycolysis, even in the presence of oxygen. The Warburg effect is controlled by oncogenes—c-Myc, Kras, P1K/AKT/mTOR pathway—and tumor suppressors—p53, LKB1/AMPK, PTEN, and RB. Studies on oncogenes and tumor suppressors suggest potential therapeutic strategies. The oncogene Kras promotes increased glucose uptake, glycolytic flux and ribose biogenesis, and mediates reprogramming of glutamine metabolism by changes in gene expression. The tumor suppressor p53 promotes the expression of antioxidant proteins that regulate oxidative stress and glucose metabolism. The LKB1/AMPK agonists have potential to be anticancer drugs, as patients treated by metformin for diabetes had a lower incidence of cancer. Discovering the mechanism by which oncogenes and tumor suppressors regulate metabolism will allow for designing treatment strategies. This review discusses how several oncogenes and tumor suppressors regulate cellular metabolism, and the current therapeutic findings.