RIGHT DRUGS AND RIGHT PATIENTS-I. PHARMACO-GENOMIC AND-GENETIC APPROACHES FOR EFFICIENT TREATMENT OF 5-FU

Abstract

5-fluorouracil (5-FU) has been used as a broad anticancer drug, however, its side effects have been monitored. Therefore, we performed pharmaco-genomic and -genetic studies for right treatment of 5-FU for right patients. As results, we found genetic polymorphisms at metabolic enzymes of 5-FU, e.g. DPYD-85, -1627, and -1896 sites, TS-5'ER, and -3'UTR, and MTHFR-222, and -429 sites among Korean populations (normal, N=105; head and neck patients, N=28). There was a significant association between TS-mRNA levels and the 3'TS-UTR genetic polymorphism (p<0.05). From 5-FU pharmacokinetic (PK) analyses, the above each genotype did not show any effects on PK parameters. However, the combination of genetic polymorphisms at the MTHFR 222T/C, DPYD 1896T/C and 3'TS-UTR showed significant differences in AUC of 5-FU and 5-FU/5-FUD ratios (p<0.01). Therefore, this study provides molecular and clinical evidences for personalized medicine of 5-FU.