NONOXIDATIVE PENTOSE-PHOSPHATE PATHWAYS AND THEIR DIRECT ROLE IN RIBOSE SYNTHESIS IN TUMORS - IS CANCER A DISEASE OF CELLULAR GLUCOSE-METABOLISM

Pentose phosphate pathways (PPP) are considered important in tumor pro liferation processes because of their role in supplying tumor cells wi th reduced NADP and carbons for intracellular anabolic processe. Direc t involvement of PPP in tumor DNA/RNA synthesis is not considered as s ignificant as in lipid and protein syntheses. Currently, PPP activity in tumor cells is measured by lactate production, which shows a modera te activity: about 4% to 7% compared with glycolysis. Recent data gene rated in our laboratory indicate that PPP are directly involved in rib ose synthesis in pancreatic adenocarcinoma cells, through oxidative st eps (< 31%) and transketolase reactions (69%). These findings raise se rious questions about the adequacy of lactate in measuring PPP activit y in tumors. We hypothesize that ribose, not lactate, is the major pro duct of PPP in tumor cells. Control of both oxidative and nonoxidative PPP may be critical in the treatment of cancer. PPP are substantially involved in the proliferation of human tumors, which raises the prosp ect of new treatment strategies targeting specific biochemical reactio ns of PPP by hormones related to glucose metabolism, controlling thiam ine intake, the cofactor of the nonoxidative transketolase PPP reactio n, or treating cancer patients with antithiamine analogues.