Pharmacogenomics of fluorouracil, irinotecan, and oxaliplatin in hepatic metastases of colorectal cancer: clinical implications.

摘要: Hepatic metastases occur in about half of patients with colorectal cancer. Since hepatic are often not accessible for surgery, chemotherapy is important. The most commonly used drugs fluorouracil, irinotecan, and oxaliplatin. Several enzymes known to be involved the catabolism anabolism these drugs, activity varies greatly between individuals. causes this variation include genetic polymorphisms, different regulation normal cancer tissue, influence on enzyme expression. varying may have an important effect outcome chemotherapy. studies confirm thymidylate synthase, thymidine phosphorylase dihydropyrimidine dehydrogenase fluorouracil therapy cancer, higher activities predicting lower treatment efficacy. Although fewer available regarding metastases, same relationship synthase observed primary was found. For other two enzymes, only a few available, but results indicate similarly that seems disadvantageous. responsible activation, metabolism mechanism action namely carboxylesterase 2, cytochrome P450 (CYP) 3A4, uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1), topoisomerase-I, also exhibit variable inter-individual activity. Thus, there association response therapy. instance, topoisomerase-I predictive better irinotecan. CYP3A4 UGT1A1 levels might irinotecan toxicity rather than degradation oxaliplatin independent potentially activity, drug, DNA repair ERCC1 survival time after Taken together, data importance More information needed, especially newer However, existing very promising respect potential guide dose drug selection more efficient less toxic metastases.