CYP450 pharmacogenetics for personalizing cancer therapy

Abstract

Today's drug therapy regimens rely on the anticipated relation between drug dose, acquired plasma level and desired effect. However, the capacity of individual patients to absorb and metabolise drugs may differ significantly, part of which is due to genetic factors. These genetic factors can be used to predict the drug metabolizing potential of patients before starting therapy. A major challenge is to identify the genetic polymorphisms which are relevant for a particular therapy and to determine the clinical consequences with respect to dosing, or choice of drug, based on the outcome of pharmacogenetic analyses. For the cytochrome P450 system, which catalyzes oxidative reactions, many new genetic polymorphisms have been identified in the last years. In this review, the current knowledge of cytochrome P450 polymorphisms with respect to cancer treatment is described, highlighting the potential of reaching considerable benefit from personalized therapy, either by improving efficacy or reducing the toxicity of current treatment regimens. This review specifically addresses the knowledge today on cytochrome P450 pharmacogenetics for tamoxifen, docetaxel, paclitaxel, cyclophosphamide, ifosfamide, imatinib, gefitinib, irinotecan, etoposide, teniposide, thalidomide and vincristine therapies, discussing its current potential for individualized therapy based on cytochrome P450 genetic polymorphisms.