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KMID : 1188520050010010045
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Korean Journal of Clinical Oncology
2005 Volume.1 No. 1 p.45 ~ p.50
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Overcoming the resistance of 5-FU through understanding the drug interaction
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Lim Hyeong-Suk
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Abstract
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5-flourouracil is widely used in the treatment of cancer. The sustained interest in 5-FU may be ascribed, to a great extent, to drug interactions by which action of 5-FU can be modulated in order to increase effectiveness and overcome resistance with decreased toxicities. Various modulators of 5-FU have been developed and have been successfully applied in clinical field. Leucovorin potenti￢ates the activity of intravenous 5-FU. Dihydropyrimidine dehydrogenase inhibitors such as uracil and gimestat have been incorporated to oral 5-FU product to increase bioavailability by inhibiting first pass metabolism during the absorption process. In various clinical studies, combinations of these modulators have been shown to be superior or equivalent in effectiveness to the single agent 5-FU with improved toxicity profiles. Resistance, innate or acquired, is the major hurdle to overcome in 5-FU therapy in the same manner with other anticancer agents. Majority of the resistances to 5-FU can be explained by the increase in thymidylate synthase which is involved in de novo pyrimidine biosynthesis. This review on 5-FU is largely on the drug interactions and on the mechanism of resistance.
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KEYWORD
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5-FU , modulator | resistance
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