Pharmacogenomics in oncology

Precision therapy in the field of oncology is rapidly developing. Numerous somatic genetic markers in eg tyrosine kinase receptors or transcription factors have been identified to be indicative for the treatment with anti-cancer drugs. In contrast, only some recommendations have been developed considering hereditary variants in drug metabolizing enzymes such as TPMT, DYPD or UGT1A1. Although a huge knowledge has been gained on the association of drug transporters variants such as ABCB1 or ABCG2 and clinical outcome, the overall data is inconsistent and the predictability of the related phenotype is low. However, there is increasing evidence that individual phenotypic differences may result not only from genetics, but also from epigenetic alterations such as histone-acetylation or DNA-methylation. Moreover,interactions with non-coding RNAs contribute to protein expression and may modulate drug action. Currently intriguing developments of novel therapeutic approaches through epigenetic drugs are emerging. The overall complexity of epigenetics in drug action is so far only little understood. Of significant importance are the consequences of mi RNA interaction for drug resistance in cancer by regulating target genes and efflux transporters. Further intriguing findings address DNAmethylation as modifier of transporter function and its consequences in cancer development and treatment. The progress of science may lead to the discovery of rare, but functionally relevant SNPs and a better understanding of multiple genomic, epigenomic as well as phenotypic factors, contributing to drug response in malignancies.