Pharmacogenetics in gastrointestinal tumors.

Treatment of gastrointestinal cancers has significantly advanced over the last few years with the introduction of effective chemotherapeutic and targeted drugs. To provide individual treatment with low toxicity on the one hand but maximum benefit on the other hand is still an unsolved problem. Interindividual variation of drug toxicity and efficacy is determined by genetic polymorphisms. The genetic approach based on single-gene (pharmacogenetics) or multi-gene (pharmacogenomics) analyses is developing as a valuable tool to design tailored therapy. This review focuses on clinically significant polymorphisms in genes involved in the metabolism of the major players in the chemotherapy of gastrointestinal cancer: fluoropyrimidines, irinotecan and platinum. In addition, first results of pharmacogenetics in targeted therapy including cetuximab and bevacizumab are discussed. The pharmacogenetic approach to individualize therapy in gastrointestinal cancers is promising, but additional larger and controlled studies are needed to justify changes of treatment strategies.