title: Liminal therapy: a strategy for the complete and selective destruction of malignant tissue in situ.
abstract: The property of aerobic glycolysis commonly possessed by malignant cells points to a weakness in oxidative metabolism which has been equated in some tumours with partial uncoupling of oxidative phosphorylation. The suggestions are made, first, that this endogenous defect may account for spontaneous cell death in situ, and, second, that its accentuation would inflict extensive tumour injury upon sensitive neoplasms. Certain drugs not in current use for the treatment of malignant disease are known to be able to interfere selectively with energy metabolism in sensitive tumours to such an extent that widespread necrotization ensues. The drugs activate an endogenous destructive mechanism that appears to require oxygen. Liminal therapy, the maintenance of continuous destructive pressure on sensitive growths in such a manner that maximal anti-tumour activity in terms of interference with energy production is not achieved at any one time, and under conditions in which the oxygen supply is only partly depleted, is put forward as a possible means of achieving complete and selective tumour destruction in vivo.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004078:Dihydralazine / Q000627:therapeutic use; D004351:Drug Resistance; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D006830:Hydralazine / Q000627:therapeutic use; D007545:Isoproterenol / Q000627:therapeutic use; D051379:Mice; D009278:Naphazoline / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010100:Oxygen / Q000502:physiology; D010101:Oxygen Consumption; D010656:Phenylephrine / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000188:drug therapy; D013997:Time Factors; D014667:Vasopressins / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014667:Vasopressins; D010656:Phenylephrine; D006830:Hydralazine; D009278:Naphazoline; D007545:Isoproterenol; D004078:Dihydralazine; D010100:Oxygen