Term
increased cellular capacity for DNA repair; cross resistance to other alkylating agents |
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decreased active transport of drug into cells and altered form of FH2 reductase (minor); tumore cells generate an increased concentration of FH2 reductase through gene amplification (major) |
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increased sythesis of thymidylate synthetase; altered affinity of TS for FdUMP; increased rate of catabolism of drug |
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depressed level of kinase required for activation leading to lack of phosphorylation and decreased inhibition of DNA synthesis; enhanced levels of deaminase that inactivates the drug |
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decreased drug activation by HGRPT; increases inactivation by alkaline phosphatase |
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reduced intracellular accumulation of drug due to increased efflux; amplification of the MDR1 gene/P170 GP (multidrug resistance MDR phenotype) |
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Definition
anthracyclines; daunorubacin, doxorubacin and mitoxantrone |
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Definition
efflux pump with 12 binding domains, major clinical pproblem |
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reduced intracellular accumulation (like P170 MDR gp); activation or enhancement of DNA repair mechanisms; increased glutathione transferase (GTS) activity |
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high levels of drug hydrolase activity (lacking in skin and lungs); tumor cell mutation, altering the sequence that is sensitive to intercalation |
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TPT (topotecan), CPT-11 (irinotecan) |
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