The discovery of curative drugs to battle cancer have eluded scientists for centuries. The promise of genomics is that it will invigorate the drug development process and produce effective and safe therapeutics. However, this dream has not yet been realized. In fact, lack of functional and causal information associated with genomics-based drug discovery has substantially increased the cost of pharmaceutical research, and delayed the translation of cancer targets to effective drugs. This is due in part to the fact that much of our current molecular and cancer biology research is not "genome-compatible". Although associative gene correlations are acquired by the thousands, we often perform experiments to distinguish causalities one gene at a time.

Our approach implements a three tier approach to accelerating drug discovery at CDDL.

• Data from several different microarray platforms (such as cDNA, CGH and NMD microarrays) are being integrated to better understand the molecular processes that play a key role in cancer and to prioritize the prime targets for drug development.
• Innovative technologies for miniaturized, highly parallel cell-based microarrays are being developed. Using the highly powerful RNA interference (RNAi) technology, it is possible to "knock-down" the function of specific gene in the human genome. By applying ultra high throughput (UHT) transfection of agents that trigger RNAi, genes can be screened at the genome scale using detailed analyses of the functional responses in living cells to determine which specific gene inhibitors produce anti-cancer effects and therefore have therapeutic utility as drug targets.
• CDDL will be used to develop and discover small molecule, antibody, and nucleic acid based agents to target the most promising gene and gene products for advancement to preclinical and clinical testing. This research is setting the stage for the ability to rapidly and effectively translate genomics into advances in anti-cancer drug development.