Cancer therapy and polymorphisms of cytochromes P450

Cytochrome P450 (CYP) enzymes are important in the metabolism of some endog enous compounds, environmental and dietary xenobiotics and many drugs. Many of these enzymes have genetic polymorphisms that produce significant chang es in metabolic activity, however the function of other polymorphisms is un known. Genetic polymorphisms have important influences on variability in hu man pharmacokinetics, including intra-individual differences in drug toxici ty, drug interactions and response to chemotherapy. Other factors that infl uence drug metabolism include differences in enzyme expression due to diffe rences in age, gender, smoking status, exposure to dietary or environmental xenobiotics or co-administration of other drugs. In addition, some xenobio tics and drugs can directly inhibit or induce the activity of CYPs. All of these factors can produce differences in metabolic capacities among individ uals which can produce toxicity in some patients and sub-effective dosing i n others. Maximum clinical benefit will require a more complete understandi ng of the influence of these polymorphisms on allele function and their int eraction with inducers and inhibitors of enzyme expression or activity. Thi s effort will permit the pharmacogenetic screening of patients before the a dministration of drugs and result in the identification of individuals who are prone to adverse reactions or poor response, resulting in more effectiv e individualized therapy.