Topoisomerase I involvement in schedule-dependent interaction between 5-fluoro-uracil and irinotecan in the treatment of colorectal cancer.
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.
Richter
Sara N
SN
Nadai
Matteo
M
Palumbo
Manlio
M
Palù
Giorgio
G
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D004264:DNA Topoisomerases, Type I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005472:Fluorouracil / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan
D000077146:Irinotecan; D004264:DNA Topoisomerases, Type I; D005472:Fluorouracil; D002166:Camptothecin