Therapeutic potential of targeting glucose metabolism in glioma stem cells

Abstract

Glioblastoma is a highly lethal cancer. Glioma stem cells (GSCs) are potentially an attractive therapeutic target and eradication of GSCs may impact tumor growth and sensitize tumors to conventional therapies. The brain is one of the most metabolically active organs with glucose representing the most important, but not the only, source of energy and carbon. Like all other cancers, glioblastoma requires a continuous source of energy and molecular resources for new cell production with a preferential use of aerobic glycolysis, recognized as the Warburg effect. As selected metabolic nodes are amenable to therapeutic targeting, we observed that the Warburg effect may causally contribute to glioma heterogeneity. This Editorial summarizes recent studies that examine the relationship between GSCs and metabolism and briefly provides our views for the future directions. The ultimate goal is to establish a new concept by incorporating both the cellular hierarchical theory and the cellular evolution theory to explain tumor heterogeneity. Such concept may better elucidate the mechanisms of how tumors gain cellular and molecular complexity and guide us develop novel and effective targeted therapies.