Pharmacogenomic Discovery Delineating the Genetic Basis of Drug Response

Abstract

Personalized medicine has the promise to tailor medical care based on the patient's genetic make-up and clinical variables such as gender, race and exposure to environmental stimuli. Recent progress in pharmacogenetic and pharmacogenomic studies has suggested that drug response to therapeutic treatments is likely a complex trait influenced by a variety of genetic and non-genetic factors. Identifying molecular targets (e.g., genetic variants) delineating the genetic basis of drug response could help understand the complex nature of drug response. The last decade has witnessed significant advances in genome-wide profiling technologies for genetic/epigenetic variations and gene expression. As an unbiased, cell-based model for pharmacogenomic discovery, a tremendous resource of whole-genome molecular targets has been accumulated for the HapMap lymphoblastoid cell lines (LCLs) during the past decade. The current progress, particularly in cancer pharmacogenomics, using the LCL model was reviewed to illustrate the potential impact of systems biology approaches on pharmacogenomic discovery.