Preface [Hot Topic: Pharmacogenomics (Guest Editor: Amadeo M. Parissenti)]

With the complete sequencing of the human and other genomes and recent technical advances such as DNA microarray analysis, comparative genomic hybridization, real-time PCR, and capillary electrophoresis, unprecedented progress is being made in understanding drug effects on the genome and the influence of the genome on drug toxicity and efficacy. This special issue of Current Topics in Medicinal Chemistry describes recent advances in the relatively new field of “pharmacogenomics”, geared specifically to the medicinal chemist. The issue begins with a review from our laboratory, outlining the theory behind DNA microarray analysis and how this technique is helping to identify genes whose expression correlates with drug response and drug resistance in living systems. Zunyan Dai and colleagues from Wolfgang Sadee's laboratory focus specifically in this issue on the use of DNA microarray and other pharmacogenomic approaches to aid in the discovery of genes (such as those involved in growth factor signaling) whose expression correlates with response to a wide variety of anti-cancer drugs. While the performance of DNA microarray experiments is not technically difficult, there are a variety of ways in which to analyze DNA microarray data. Hubert Hackl and colleagues from Zlatoko Trajanoski's laboratory describe current methods for the analysis of microarray data and provide an understanding of the challenges associated with interpreting large data sets. Pharmacogenomic approaches can also be used to help optimise response to non-drug therapies. Bapat and Mishra describe the application of genomics and bioinformatics to optimize stem cell therapy. In addition to the effect of gene expression on drug response, variations in gene structure, such as small nuclear polymorphisms (SNPs), can also influence drug response in living systems. Sakaeda and colleagues from Katsuhiko Okumura's laboratory focus specifically on drug transporters such as P-glycoprotein and how polymorphisms in genes coding for drug transporters can affect drug pharmacodynamics and hence patient response to specific drugs. Fabienne Thomas and colleagues review the role of SNPs in a variety of genes affecting drug efficacy in patients, including those coding for drugmetabolizing enzymes, drug transporters, and proteins involved in DNA repair. Similarly, SNPs can also have a major effect on drug toxicity. Cuneyt and Spigset describe a variety of genetic and non-genetic factors that affect drug toxicity, and the need for large-scale studies to determine the relative contribution of genetic and environmental factors on adverse reactions to drugs. The field of pharmacogenomics is also impacting the drug discovery process. Richard Twyman describes how large-scale association studies between specific SNPs and disease incidence can help uncover and / or eliminate possible drug targets. Moreover, SNP data can be used in drug development by identifying those structures that work efficiently over a broad group of affected individuals or are only effective for patients with specific genotypes. As an example, David Moskowitz and Frank Johnson describe associations with specific ACE genotypes and both disease incidence and response to therapy. In addition to its scientific promise, the field of pharmacogenomics will likely yield numerous benefits for the pharmaceutical and biotechnology industries, including decreasing the size and expense of clinical trials and streamlining the drug development process. Dr. Amalia Issa describes how the field of pharmacogenomics is impacting on policies and regulatory processes by national bodies such as the Food and Drug Administration.. In summary, it is becoming increasingly clear that pharmacogenomic approaches are having a major impact on every aspect of medicinal chemistry. These include screening lead compounds, identifying optimal structures, revealing mechanisms associated with drug response and resistance, tailoring therapies to optimize therapies and minimize toxicity, and developing policies that incorporate pharmacogenomics-based drug development into regulatory processes. Thus, this special issue of Critical Reviews of Medicinal Chemistry is both highly significant and timely.