Towards a metabolic therapy of cancer?

Abstract

Abstract. It is increasingly appreciated that cancer cells must be endowed with specific metabolic adaptations to support enhanced growth and to ensure survival under stressful conditions. On the other hand, many oncogenic mutations of protooncogenes and tumor suppressor genes directly cause metabolic derangements and, conversely,mutations of enzymes have been found to underlie several forms of cancer. Thus, cancer-specific metabolic alterations are now considered among the hallmarks of malignant tumors. Most commonly, cancer cells exhibit enhanced glycolysis under aerobic conditions (the Warburg effect) but alterations in the metabolism of amino acids, such as glutamine, serine and proline are increasingly described as important metabolic features of selected tumor types. In theory, all these deranged cancer-specific metabolic pathways may constitute novel therapeutic targets, although the only “metabolic” drug in clinical use is still represented by the enzyme L-asparaginase. However, the increasing amount of experimental evidence, as well as the number of trials in progress, suggests that metabolic drugs will soon complement standard anti-cancer chemotherapy and modern biological drugs.