Modeling primary sugar metabolism in neuroblastoma to identify central nodes for therapeutic intervention
Enhanced conversion of glucose to lactic acid in the presence of oxygen (“aerobic glycolysis”), also known as Warburg effect, is a common biochemical feature of cancer cells acquired during cancer formation. This does not only serve as the main source of energy, but is mainly required for generation of metabolic intermediates in rapidly dividing cancer cells.
Recently, the finding that altered metabolic conditions in tumors might give rise to new therapy options have fueled scientific research activities. Many tumor types use different enzyme variants of hexokinase, a key enzyme of glycolysis. This variant, designated hexokinase II, was shown to be important for tumor maintenance. We already demonstrated that neuroblastomas, aggressive tumors of the nervous system in infants and children, upregulate hexokinase II, too. To obtain deeper insights in the sugar metabolism of neuroblastoma, we will determine enzymatic activities of enzymes converting sugar (glucose) to lactic acid. In cooperation between biochemists, tumor biologists and bioinformaticians, models will be established explaining the altered sugar metabolism in tumor cells. Since several lines of evidence indicate that inhibiting glycolysis can sensitize cancer cells to other treatment modalities, we hope that these models could provide the rationale for developing novel targeted therapies.
Keywords: Neuroblastoma, Primary Sugar Metabolism