%0 Journal Article
%T Pharmacogenomics: a key component of personalized therapy
%A Matthias Schwab
%A Elke Schaeffeler
%J Genome Medicine
%D 2012
%I BioMed Central
%R 10.1186/gm394
%X It is beyond doubt that pharmacogenomics promotes the development of targeted therapies, as was demonstrated by the approval earlier this year of the drug ivacaftor by the US Food and Drug Administration (FDA) and the European Medicines Agency for the treatment of a subset of cystic fibrosis patients. Ivacaftor is approved only for cystic fibrosis patients bearing the specific G551D genetic variant in the cystic fibrosis transmembrane regulator (CFTR) gene, which encodes a protein that regulates chloride and water transport in the body and is defective in the disease. Ivacaftor targets the CFTR protein, increases its activity, and consequently improves lung function [3].Although this and other examples (such as vemurafenib as an inhibitor of the BRAF V600E mutation in malignant melanoma [1]) suggest the demise of the blockbuster model of drug development, the concept of targeted therapy is in its early stages. One reason is that monogenic pharmacogenetic traits are mostly unable to explain the variations in a complex phenotype such as drug response [2]. There is evidence through drug-target network analyses that most currently used drugs have multiple targets and numerous off-target effects. Genome-wide approaches such as sequencing, epigenomic profiling and metabolomics will be essential for understanding the detailed molecular architecture of disease etiology and/or drug response. Genome-wide association studies (GWAS) have implicated many new biological pathways, but this approach has limitations because most of the variants that have been associated with clinical phenotypes, such as adverse drug reactions, are not necessarily causal.There is reasonable hope that pharmacogenomic research will benefit from a combination of different omics technologies. Recently, multi-omics studies have shown their use in discovering potential novel therapeutic targets [1]. For instance, in one multi-omics study the integrative personal omics profile (iPOP), which combines genomic
%U http://genomemedicine.com/content/4/11/93