Abstract
5-Fluoro-uracil (5FU), an antimetabolite drug, stimulates expression of topoisomerase I (tpI) in adenocarcinoma cancer cells. When 5FU is given in combination with Irinotecan (IR), a tpI poison, the most effective regimen is represented by IR given before low doses of 5FU. Hence, despite their distinct mechanisms of action, the molecular basis for successful combination and schedule of 5FU and IR in the treatment of colorectal cancer rests on the opposing drug effects on the expression and poisoning of the tpI enzyme.
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / enzymology
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Camptothecin / administration & dosage
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Camptothecin / analogs & derivatives
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Cell Line, Tumor
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / enzymology
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DNA Topoisomerases, Type I / drug effects
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DNA Topoisomerases, Type I / genetics
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DNA Topoisomerases, Type I / metabolism*
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Drug Administration Schedule
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Drug Interactions
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Fluorouracil / administration & dosage
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Irinotecan
Substances
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Irinotecan
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DNA Topoisomerases, Type I
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Fluorouracil
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Camptothecin