PROPOSED TREATMENT OF CANCER BY INHIBITION OF GLUCONEOGENESIS

Increased anaerobic glucose consumption is a constant finding incancer cells and is apparently essential for primary tumor growth andprogression. The combination of anaerobic tumor energy productionand reconversion of the resulting lactate (and other precursors) toglucose via gluconeogenesis in normal tissues, is considered to con-stitute a 'metabolic circuit by means of which the body is depleted ofits energy reservoirs and the process of cachexia maintained. Gluconeo-genesis inhibition is proposed as a measure which could interrupt theimmediate process of cachexia, while in conjunction with a low car-bohydrate diet severely restrict glucose from the cancer cell and thusinhibit tumor energy production and growth. Use of L-tryptophan isproposed as the primary anti-gluconeogenic agent, with inhibitoryaction at the PEP carboxykinase level. The primary therapeutic aimwould be the administration of anti-gluconeogenic substances in anamount sufficient to completely halt gluconeogenesis, and use of die-tary carbohydrate as a means of controlling the desired blood glucoselevels. The special significance of lactate as a precursor substrate ingluconeogenesis in cancer patients, especially in regard to the bio-chemical mechanisms of cachexia, is discussed, as well as lactate in-hibition by 2-mercaptopropionic acid and gluconeogenesis inhibitionby hepatotoxic agents. The prevention of glucose utilization once glu-cose enters the cancer cell is a secondary therapeutic aim, mediated byuse of hexokimse inhibitors, glucose analogs, and specific inhibitionof enzyme systems in the Embden-Meyerhof pathway. Insulin andinsulin-dependent hypoglycemic agents are viewed as potentially ha-zardous compounds in a hypoglycemic regimen, since insulin canpromote the excessive utilization of glucose within the cancer cell. © 1968 S. Karger AG, Basel.