The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites

• Published in: Molecular cancer therapeutics Vol. 4; no. 5; pp. 855 - 863
• Main Authors: Pratt, Susan, Shepard, Robert L., Kandasamy, Ramani A., Johnston, Paul A., Perry, William, Dantzig, Anne H.
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01.05.2005
• Subjects: 5-fluorouracil; Adenosine Triphosphate - pharmacology; Antimetabolites, Antineoplastic - pharmacokinetics; Antimetabolites, Antineoplastic - pharmacology; Apoptosis - drug effects; Biological Transport - drug effects; Cells, Cultured; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Floxuridine - metabolism; Fluorouracil - pharmacokinetics; Fluorouracil - pharmacology; Humans; Kidney - cytology; Kidney - drug effects; Kidney - metabolism; Metabolites; MRP-5 (ABCC5); Multidrug resistance protein; Multidrug Resistance-Associated Proteins - metabolism; Phosphorylation - drug effects; Thioguanine - pharmacology; Thymidylate Synthase - metabolism

5′-Fluorouracil (5-FU), used in the treatment of colon and breast cancers, is converted intracellularly to 5′-fluoro-2′-deoxyuridine (5-FUdR) by thymidine phosphorylase and is subsequently phosphorylated by thymidine kinase to 5′-fluoro-2′-dUMP (5-FdUMP). This active metabolite, along with the reduc...