Genotyping and phenotyping cytochrome P450: Perspectives for cancer treatment

As most anticancer agents display a narrow therapeutic window, patients may be susceptible to (extreme) toxicities or a lowered therapeutic outcome if not dosed adequately. Therefore, it is important to study factors which affect the pharmacokinetics and pharmacodynamics of these drugs. Among these, the contribution of genetic variation in drug metabolizing enzymes on the metabolism of anticancer agents has gathered interest, as it may potentially explain a substantial amount of interpatient variability in pharmacokinetics and drug response. Cytochrome P450, an oxidative enzyme-system involved in the breakdown of many drugs, is currently studied for correlations between genetic polymorphisms and anticancer drug metabolism. Also, alternative ways to predict the expression of cytochrome P450 have been developed (phenotyping measures) which may have additional value in creating a lowered interpatient variability, to minimize side-effects and maximize therapeutic efficacy. (c) 2005 Elsevier Ltd. All rights reserved.