The Sidney Kimmel Cancer Center (SKCC) is a growing institution with the mission to conduct basic biological research to understand the mechanisms of cancer and to translate target discoveries in the laboratories to the treatment of patients. Twenty faculty members conduct research programs at SKCC and over half are funded by NCI. The best tools available in the molecular dissection of cancer biology and therapy are necessary to meet current NCI goals of defining cancer in molecular terms (NCI - Molecular Profiling Initiative). The shared resources specifically requested are intended to run a proteomic facility being outfitted by SKCC with nearly $1 million dollars of equipment including mass spectrometers, 2D gelsystem, HPLC, differential protein analysis software and high-speed computers. The goal of numerous SKCC investigators is to characterize the molecular properties of tumor cells, including specific stages of tumor progression, and to compare the properties of different tumors of the same and dissimilar types. The ability to evaluate individually selected cells, specific clusters of cells from a tumor specimen or specific organelles in specific cell types in the tumor has been extremely difficult until recent new advances, some developed by SKCC scientists, including: novel tissue subfractionation techniques, improved laser capture microdissection, and improved differential gene expression assays. The SKCC Genomic Core Facility requires complementary data at the protein level using new robust proteomic techniques permitting not only rapid single protein identification but also simultaneous analysis of hundreds to thousands of proteins. Proteomic analysis coupled with cDNA array analysis of differential gene expression provides a powerful set of shared resources for SKCC investigators to probe the molecular and genetic properties of cancer cells. The numerous basic and clinical research projects described in this application show the need of these services by our investigators. Major goals include the identification of new diagnostic and therapeutic targets for clinical progression and a better understanding of the processes of cancer development and metastatic progression. Basic studies finding new cancer targets through combining genomics and proteomics are essential for combating cancer. Finding tumor targets that are accessible to agents injected into blood has obvious therapeutic benefits and may not be particularly accessible to genomic analysis but may be best pursued through a novel SKCC strategy requiring proteomic analysis. Clinical studies acquiring proteomic and genomic maps for pairwise sample comparisons may reveal patterns of expression which are associated with the clinical phenotype of responsiveness or resistance to therapy. Such data may be of value in predicting prior to entry into subsequent trials of each therapy whether a patient has the responsiveness or resistance phenotype to the therapy. Operating a Proteomic Core Facility that combines SKCC strengths in basic and translational cancer research will provide a unique platform for target discovery in the pursuit of the cure of many cancers.
