Implications of cytochrome P450 genetic polymorphisms on the toxicity of antitumor agents.
In the treatment of cancer, a narrow therapeutic window generally exists between toxicity and suboptimal therapy. In addition, interindividual variation in drug metabolism seriously complicates therapy. Genetic polymorphisms in phase 1 and phase 2 enzymes are present in the population and may explain part of the observed interindividual variation in drug pharmacokinetics. For the cytochrome P450 superfamily, information on variant alleles encoding enzymes with decreased activity is rapidly on the increase. The potential of applying pharmacogenetic screening before therapy in the treatment of cancer seems to be greatest for CYP2B6 (cyclophosphamide treatment), CYP2C8 (paclitaxel therapy), and CYP3A5; however, the drugs of interest still need to be identified for this latter enzyme.
van Schaik
Ron H N
RH
Department of Clinical Chemistry, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. r.vanschaik@erasmusmc.nl
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D005787:Gene Frequency; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011110:Polymorphism, Genetic
D000970:Antineoplastic Agents; D003577:Cytochrome P-450 Enzyme System