MODIFICATION OF TUMOR GLUCOSE-METABOLISM FOR THERAPEUTIC BENEFIT

Tumours have a much greater dependence than normal tissues on anaerobi c glycolysis for energy generation, We have studied the effects of gly colysis inhibition on tumour cells in vitro. Cellular ATP fell during exposure of cells in air to 2-deoxy glucose or to the lactate dehydrog enase inhibitor oxamate, Glycolysis inhibition alone did not alter clo nogenic cell survival over 6 h, but a 6-h exposure to oxamate combined with doxorubicin (Dox) gave greater than additive cell killing. This effect was greatest when oxamate was dosed after Dox, suggesting that oxamate inhibited repair of Dox-induced damage, Oxamate also gave grea ter than additive cell killing in multicellular spheroids when combine d with Dox and there was a greater than additive growth delay in spher oids dosed,vith Dox plus oxamate. These data demonstrate that inhibiti on of anaerobic glycolysis might be used to obtain a significant thera peutic gain in combination treatments with cytotoxic drugs or radiothe rapy.