gms | German Medical Science

Inter-individual differences in tumor response and toxicity after chemotherapy are still a common phenomenon. Genetic polymorphisms have been identified to be responsible for these differences. Pharmacogenetic analyses evaluate the impact of DNA-variants (polymorphisms) on enzyme function in proteins involved in metabolic processes of the administrated drugs. Recently, pharmacogenetic approaches in several tumors discovered multiple associations between single polymorphism or polymorphism patterns and clinical endpoints like survival, tumor response and toxicity. For example a pattern of four polymorphisms in metabolic genes potentially discriminate between colorectal cancer patients that will and those that will not benefit from a 5-FU/oxaliplatin chemotherapy. The constantly growing armamentarium of effective therapeutics is the basis for the incorporation of this knowledge of individual genotype-driven drug metabolism into the management of patients. Due to similar effective drugs (e.g. in colorectal tumors) we arepotentially enabled to provide effective treatment to a patient, based on the patient’s genetic profile. First clinical studies are initiated worldwide assigning patients to a specific drug or drug combination based on their genetic background aiming to provide a treatment of maximum benefit and minimal side effects. In addition to the optimization of traditional chemotherapy pharmacogenetics will be essential to identify candidate patients for targeted therapies. The number of drugs that target a specific structure e.g. on the cell surface is growing rapidly. We learned that norm-variants of essential proteins exist in nature, but only a certain genetic determination assures efficacy of the drug. For example almost exclusively lung cancer patients that possess specific activating mutations within the EGFR gene will response to tyrosine kinase inhibition. Despite encouraging results from pharmacogenetic studies, we are still in the beginning of translating laboratory progress into valuable tools for oncologists in clinical practise. Limitations include small sample number, the mostly retrospective character of performed analyses and varied source of material used for the experiments. But overall pharmacogenetics appears as a promising tool to further support and guide the choice of treatment for the individual patient.