Modulation of cytochrome P450 activity: implications for cancer therapy

Abstract

Although metabolism mediated by cytochrome P450 isoenzymes is known to play a major part in the biotransformation of anticancer agents in vivo, few clinical studies have investigated activity of cytochrome P450s and therapeutic outcome in people with cancer. Variability between individuals in the pharmacokinetics of cancer chemotherapy has important consequences in terms of therapeutic efficacy and safety. We discuss here the effect of drug metabolism mediated by cytochrome P450 on therapeutic outcome. As examples, the biotransformation pathways of cyclophosphamide, ifosfamide, tamoxifen, docetaxel, paclitaxel, and irinotecan are discussed. Since most anticancer agents are transformed by enzymes, better knowledge of their metabolic pathways could help improve treatment outcome and safety. Furthermore, a more complete understanding of the metabolism of anticancer agents through phenotyping and genotyping approaches will facilitate the prediction of interactions between drugs. More clinical evidence is needed on the metabolic transformation and drug interactions with these agents to improve cancer therapeutics.