Cancer treatment and pharmacogenetics of cytochrome P450 enzymes

For the treatment of cancer, the window between drug toxicity and suboptimal therapy is often narrow. Interindividual variation in drug metabolism therefore complicates therapy. Genetic polymorphisms in phase I and phase II enzymes may explain part of the observed interindividual variation in pharmacokinetics and pharmacodynamics of anticancer drugs. The cytochrome P450 superfamily is involved in many drug metabolizing reactions. Information on variant alleles for the different isoenzymes of this family, encoding proteins with decreased enzymatic activity, is rapidly growing. The ultimate goal of ongoing research on these enzymes would be to enable pharmacogenetic screening prior to anticancer therapy. At this moment, potential clinically relevant application of CYP450 pharmacogenetics for anticancer therapy may be found for CYP1A2 and flutamide, CYP2A6 and tegafur, CYP2B6 and cyclophosphamide, CYP2C8 and paclitaxel, CYP2D6 and tamoxifen, and CYP3A5. For this latter enzyme, the drugs of interest still need to be identified.