Recent advances in the design of anticancer chemotherapy.
Recent advances in the rational design of anticancer chemotherapy in this laboratory have been based on strategic differences between normal and cancer cells. On the basis of our identification of quantitative biochemical markers and characteristic enzymic and metabolic programs of neoplastic cells, we have designed single and combination drug treatments. This chemotherapeutic approach aims at specific enzymic targets in cancer cells that are closely linked with transformation and progression. With the identification of markedly increased concentrations of CTP, dATP, dGTP, dCTP and dTTP in neoplasms, there should be an operational advantage in directing chemotherapy to depress the concentration of these metabolites elevated in cancer cells, because a drug-imposed curtailment of these metabolites might destroy cancer cells that depend more stringently on the increased concentrations of these nucleotides. Experiments in tissue culture and in solid tumors utilizing treatment schedules with pyrazofurin in combination with galactosamine, and the use of adriamycin, succeeded in achieving profound alterations in the nucleotide concentrations of cancer cells.
D000577:Amides; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003854:Deoxyribonucleotides / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004358:Drug Therapy / Q000639:trends*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism*; D011720:Pyrazoles; D051381:Rats; D012263:Ribonucleosides / Q000494:pharmacology*; D012265:Ribonucleotides / Q000378:metabolism; D012266:Ribose; D013937:Thymidine Kinase / Q000378:metabolism
D000577:Amides; D000970:Antineoplastic Agents; D003854:Deoxyribonucleotides; D011720:Pyrazoles; D012263:Ribonucleosides; D012265:Ribonucleotides; C002997:pyrazofurin; D012266:Ribose; D004317:Doxorubicin; D013937:Thymidine Kinase