Use of Metabolic Control Analysis to Design a New Strategy for Cancer Therapy

The synthesis of nucleic acids is much more active in cancer than in normal cells, and is a process of the utmost importance in tumour proliferation. At present, conventional cancer treatment is directed only at the inhibition of synthesis of the purine and pyrimidine bases. Antimetabolites and alkylating agents are cancer chemotherapeutic agents that inhibit nucleic acid synthesis by preventing the synthesis of substrates for only half of the nucleic acid molecule, namely the purine and pyrimidine bases. It has been well known since the 193os that glucose metabolism is increased in malignant tissues (Warburg, 1930, 1956). The increase in glucose metabolism is accompanied not only by an increase of lactate production but also by an increase in pentose production for RNA and DNA synthesis (Eigenbrodt et al., 1985).However, the importance of the pentose phosphate pathway in tumours has been overlooked.