Ethnic differences in the metabolism, toxicology and efficacy of three anticancer drugs

Abstract

Large inter-individual and inter-ethnic differences are observed in efficacies and toxicities of medical drugs. To improve the predictability of these differences, pharmacogenetic information has been applied to clinical situations. Expanding pharmacogenetic information would be a valuable tool to the medical community as well as the patient to fulfill the promise of personalized anticancer drug therapy. This review highlights genetic polymorphisms and ethnic differences of genes, UGT1As, CYP3A4, CES1As, ABCB1, ABCC2, ABCG2, SLCO1B1, CDA and CYP2D6, involved in metabolism and disposition of three anticancer drugs: irinotecan, gemcitabine and tamoxifen. Recent pharmacogenetic studies have successfully identified distinct ethnic differences in genetic polymorphisms that are potentially involved in efficacies and toxicities of anticancer drugs. This achievement has led to personalized irinotecan therapy, reflecting ethnic differences in UGT1A1 genotypes, and possible benefits of genetic testing have also been suggested for gemcitabine and tamoxifen therapy, which still requires further validation. The ultimate goal for patients is a high rate or even perfect prediction of efficacies and toxicities of anticancer drugs in each ethnic population. For this challenge, more clinical studies combined with comprehensive omics approaches are necessary to further advance the field.