Abstract
As long as it is impossible to prevent or to correct the altered expression of genetic information in malignant cells, tumor chemotherapy has to aim at the elimination of malignant cells by means of cytostatic or cytocidal drugs that are as selective as possible for a given tumor. The minimal difference in the sensitivity of normal and neoplastic cells remains a critical limitation in the use of effective agents, many of which are antimetabolites that inhibit enzymes of essential metabolic pathways on the basis of a structural similarity with physiological intermediates, interfering thereby with cellular growth and proliferation. This may be illustrated by the blockade of thymidylate synthetase induced by 5-fluoro-5′-deoxyuridinemonophosphate (FdUMP), a metabolite of the pyrimidine analog 5-fluorouracil (reviewed by Heidelberger [5]. The consequent depletion of deoxythymidine-5′-monophosphate (dTMP) and deoxythymidine-5′-triphosphate (dTTP) pools should result in DNA synthesis inhibition due to substrate deficiency. This is one of several mechanisms by which fluorinated pyrimidines preferentially inhibit proliferating cells. This effect may be circumvented, however, by dTMP formation from deoxythymidine on the salvage pathway, and this underlines the critical importance of quantitative metaboliteantimetabolite relationships in tumor chemotherapy.
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References
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© 1986 Springer-Verlag Berlin · Heidelberg
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Keppler, D., Holstege, A. (1986). Biochemical Basis for Improving Chemotherapeutic Regimens in Liver Malignancies. In: Herfarth, C., Schlag, P., Hohenberger, P. (eds) Therapeutic Strategies in Primary and Metastatic Liver Cancer. Recent Results in Cancer Research, vol 100. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-82635-1_15
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DOI: https://doi.org/10.1007/978-3-642-82635-1_15
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