The Use of DNA Microarrays to Investigate the Pharmacogenomics of Drug Response in Living Systems

David   J.   Villeneuve; Amadeo   M.   Parissenti

Abstract

With the advent of DNA microarray analysis, it is now possible to examine the response of virtually the entire human genome to cellular drug exposure and to uncover a wide variety of genes correlating with the establishment of drug resistance. This relatively new field of “pharmacogenomics” is likely to vastly increase our understanding of the mechanisms of drug action and how cells respond and adapt to drug exposure. However, DNA microarray studies typically result in the identification of hundreds of genes that may or may not be of relevance in vivo --- particularly when large, genetically diverse study populations are used. The challenge to the researcher is to design experimental systems and approaches which minimize variability in the data, increase the reproducibility amongst experiments, allow array data from multiple experiments to be assessed by a variety of statistical, supervised learning, and data clustering approaches, and provide a clear link between drug response and the expression of specific genes. This review provides a description and critical analysis of recent studies on the pharmacogenomics of drug response and discusses current guidelines and approaches for the performance and analysis of DNA microarray experiments in this area.

Keywords: pharmacogenomics, dna microarray, chemotherapy, drug response, drug resistance, miame standards, review