Genetic Polymorphisms of Drug-Metabolising Enzymes and Drug Transporters in the Chemotherapeutic Treatment of Cancer

摘要: There is wide variability in the response of individuals to standard doses drug therapy. This an important problem clinical practice, where it can lead therapeutic failures or adverse reactions. Polymorphisms genes coding for metabolising enzymes and transporters affect efficacy toxicity. Pharmacogenetics aims identify predisposed a high risk toxicity low from anti-cancer drugs. review focuses on significance polymorphisms drug-metabolising (cytochrome P450 [CYP] 2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, dihydropyrimidine dehydrogenase, uridine diphosphate glucuronosyltransferase [UGT] 1A1, glutathione S-transferase, sulfotransferase [SULT] N-acetyltransferase [NAT], thiopurine methyltransferase [TPMT]) (P-glycoprotein [multidrug resistance 1], multidrug protein 2 [MRP2], breast cancer [BCRP]) influencing chemotherapy. The most example demonstrate influence pharmacogenetics therapy TPMT. A decreased activity TPMT, caused by genetic TPMT gene, causes severe with mercaptopurine. Dosage reduction necessary patients heterozygous homozygous mutation this gene. Other showing chemotherapeutic treatment are discussed, such as UGT1A1*28. polymorphism associated increase irinotecan. Also, DPYD gene show relation fluorouracil-related toxicity; however, cases no clear association has been found transporters, pharmacokinetics pharmacodynamics studies discussed evaluate different regimens tumour types that have different, sometimes even contradictory, pharmacokinetic pharmacodynamic effects tumours application will therefore require more detailed information transporters. Larger studies, ethnic populations, extended haplotype linkage disequilibrium analysis, be each separately.