[Acquisition of resistance associated with impairment of metabolic activation of anticancer drugs].
Some of anticancer drugs must undergo bioactivation in order to exert their anticancer activity. Those include most of antimetabolites, mitomycin C, cyclophosphamide and a camptothecin analog CPT-11. The latter two drugs are usually activated in liver or plasma, and the others are converted to active metabolites in the target cells. A number of biochemical mechanisms of resistance have been proposed and for the drugs to be activated in cancer cells impairment of activation enzymes were reported as one of the mechanisms; for example, deoxycytidine kinase for cytarabine and gemcitabine, orotate phosphoribosyl transferase for 5-fluorouracil, hypoxanthine-guanine phosphoribosyl transferase for 6-mercaptopurine, folylpolyglutamate synthetase for methotrexate and DT-diaphorase for mitomycin C were concerned.
Tashiro
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Cancer Chemotherapy Center, Japanese Foundation for Cancer Research.
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001711:Biotransformation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology
D000970:Antineoplastic Agents