COMBINATORIAL APPROACHES TO TREAT NEOPLASTIC DISEASES

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The central goal of this program is to continue the development of an extensive collection of small molecule combinatorial libraries, and to use these libraries in cell-based screening assays for the design and new therapeutics for cancer. Four well-established senior investigators, each directing their own project, and three cores are involved in small combinatorial libraries for molecules that trigger cytotoxic T cells and may be effective as vaccines against selected cancers. The third project will screen other small molecule, heterocycle, peptidomemetic, and organic libraries for other compounds that might control abnormal cell cycle events, and similarly, the fourth project will explore libraries to identify compounds that affect various steps in the apoptosis pathway. Immune suppression, abnormal cell cycle check points, and dysregulation of normal programmed cell death mechanisms are frequently involved in the pathogenesis of tumors. Aside from an administrative core, the program also includes to specialized cores specifically designed to produce, distribute and track synthetic libraries that currently exist, as well as an additional set of diverse combinatorial biology libraries that have recently been made available. Information and individual compounds resulting from these studies will provide important insights into the general problem of vaccine design based on small molecules, and in drug design for the regulation of abnormal cell division and altered events in the apoptosis pathway that are characteristic of malignant cells.