Biochemical Strategy of Cancer Cells and the Targeting of Chemotherapy with Tiazofurin, Acivicin, and Dipyridamole
It is 25 years since I introduced the ideas of the molecular correlation concept as a theoretical and experimental method for discovering the pattern of biochemical imbalance and its link with neoplastic transformation and progression (1). This approach was tested through application of the concept of key enzymes in a particularly meaningful model system, the rat hepatomas of different growth rates. The testing of the molecular correlation concept proved that the biochemical strategy of the genome in neoplasia can be identified by elucidating the pattern of gene expression as revealed in the activity, amount, and isozymic program of the key enzymes. It was shown that the activities of the key enzymes and metabolic pathways and the concentrations of strategic nucleotides and amino acids are stringently linked with neoplastic transformation and progression. Parameters that are not stringently linked yield no pattern. The conclusion was drawn that what is important about cancer is ordered; what is not, is the random element and the diversity. This field was recently reviewed (2,3).
KeywordsRibonucleotide Reductase Glutamine Metabolism Pyrimidine Metabolism Purine Biosynthesis Biochemical Strategy
Unable to display preview. Download preview PDF.
- 8.T. Ikegami, Y. Natsumeda, and G. Weber, Decreased Concentration of Xanthine Dehydrogenase (EC 188.8.131.52), submitted for publication (1986).Google Scholar
- 9.N. Prajda, Biochemical Phenotype in Human and Animal Liver Tumors, Proc. 13th International Cancer Congress, Part D, Research and Treatment, A. R. Liss, Inc., New York (1983).Google Scholar
- 20.R. C. Jackon, M. S. Lui, T. J. Boritzki, H. P. Morris, and G. Weber, Purine and Pyrimidine Nucleotide Patterns of Normal, Differentiating and Regenerating Liver and Hepatomas in Rats, Cancer Res. 40: 1286 (1980).Google Scholar
- 25.G. Gebeyehu, V. E. Marquez, A. C. Van Cott, D. A. Cooney, J. A. Kelley, H. N. Jayaram, G. S. Ahluwalia, R. L. Dion, Y. A. Wilson, and D. G. Johns, Ribavirin, Tiazofurin, and Selenazofurin; Mononucleotides and Nicotinamide Adenine Dinucleotide Analogs, Synthesis, Structure and Interactions with IMP Dehydrogenase, J. Med. Chem. 28: 99 (1985).PubMedCrossRefGoogle Scholar
- 26.D. A. Cooney, H. N. Jayaram, R. I. Glazer, J. A. Kelley, V. E. Marquez, G. Gebeyehu, A. C. Van Cott, L. A. Zwelling, and D. G. Johns, Studies on the Mechanism of Action of Tiazofurin Metabolism to an Analog of NAD with Potent IMP Dehydrogenase-inhibitory Activity, Adv. Enz. Reg. 21: 271 (1983).CrossRefGoogle Scholar
- 28.G. Weber, M. S. Lui, J. Sebolt, and M. A. Faderan, Molecular Targets of Anti-glutamine Therapy with Acivicin in Cancer Cells, in: “Glutamine Metabolism in Mammalian Tissues, ” D. Häussinger and H. Sies, eds., Springer Verlag, Heidelberg (1984).Google Scholar