Summary
One of the important goals of cancer research is to understand the nature of gene expression regulation and biological pathways and to apply this knowledge to find the mechanism by which small drug molecules interfere with the biological system through interactions with gene products and pathways. We have utilized the gene expression and small molecule screening data available at the National Cancer Institute (NCI) for 60 immortalized cell lines representing a range of major cancers. This extensive data set potentially contains the complete information necessary to understand and target cancer cells. In our experience it is most fruitful to adopt systems biology and pharmacogenomic approaches to deconvolute the necessary chemistry and biology in order to conduct a rational anti-cancer drug design effort. In this undertaking, existing biological pathway and gene expression information is merged with drug chemosensitivity data to both elucidate a drug’s mechanism of action and to find cancer-specific targets. This framework offers a rational design strategy to mine novel anti-cancer candidates that are both potent and show specificity to targets in cancer pathways.