Systems biology in drug safety and metabolism: integration of microarray, real-time PCR and enzyme approaches.
The last decade has seen a rapid expansion in the field of functional genomics, due mainly to the global gene expression profiling capabilities provided by techniques, such as microarray analysis. Application of these technologies in fields as diverse as plant research, to public health and environmental sciences, forensic science and drug research, shows the versatility of these tools and the promise they hold for revolutionizing research in the life sciences. In drug discovery, attempts have been made to use functional genomics in target identification and validation, lead selection and optimization, and in preclinical studies to predict clinical outcome. These studies have provided a plethora of data and undoubtedly expanded our understanding of genetic alterations in diseased and non-diseased states, but the benefits that these technologies hold have not yet been fully realized. This review discusses how a comprehensive approach to gene regulation studies, a 'systems biology' approach, is being applied in a drug development setting to address mechanism-based questions and issues raised by regulatory authorities.
Yengi
Lilian G
LG
Wyeth Research, Drug Metabolism Division, Drug Safety and Metabolism, 500 Arcola Road, Collegeville, PA 19426, USA. yengil@wyeth.com
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics / Q000379:methods* / Q000639:trends; D016133:Polymerase Chain Reaction / Q000379:methods; D040901:Proteomics / Q000379:methods; D049490:Systems Biology / Q000379:methods* / Q000639:trends; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System