This project is a major part of the Developmental Therapeutics Program drug discovery and development program within the Division of Cancer Treatment and Diagnosis. The emphasis is on preclinical drug discovery and preclinical drug development. LABORATORY OF FUNCTIONAL GENOMICS (LFG) The Laboratory of Functional Genomics (LFG) provides dedicated research support for the Screening Technologies Branch (STB), Developmental Therapeutics Program (DTP), drug discovery and development effort. Genomic techniques, including oligonucleotide microarrays, TaqMan(R) real-time PCR, reporter gene assays, mutiplexing gene assays, and RNAi are used as tools to determine the role of specific genes in the mechanisms of drug action. These methods have provided an important resource to probe for preliminary insights into mechanism of action of novel agents, or detailed analyses with preclinical drugs at a more advanced stage. The laboratory offers a resource for small businesses or extra- and intramural scientists to collaborate in an effort to bring new drugs to the clinic. Moreover, the expertise gained in this area has allowed the laboratory to play a critical role in proposing a large-scale project centered on gene profiling of drug responses in the NCI-60 cell line screen. In addition, the LFG provides preclinical, in vitro drug combination studies for evaluation of possible desirable or undesirable interactions for potential clinical drug combinations, as requested by DTP or the Clinical Therapy Evaluation Program (CTEP).