COMBINATORIAL APPROACHES TO TREAT NEOPLASTIC DISEASES

该计划的核心目标是继续开发一个 广泛收集小分子组合文库，并使用 这些文库在基于细胞的筛选试验中用于设计和新的 癌症的治疗方法。四名资深调查员， 指导他们自己的项目，三个核心参与了小 用于触发细胞毒性T细胞的分子的组合文库， 可能是有效的疫苗对选定的癌症。第三个项目 将筛选其他小分子、杂环、肽类、有机 可能控制异常细胞周期的其他化合物的库 同样，第四个项目将探索图书馆， 鉴定影响细胞凋亡途径中各个步骤的化合物。 免疫抑制、细胞周期检查点异常和免疫调节异常 正常的程序性细胞死亡机制经常参与 肿瘤的发病机制。除了一个行政核心，该计划 还包括专门设计用于生产的专用芯， 分发和跟踪目前存在的合成库，以及 另外一组不同的组合生物学文库， 最近已经可以使用了。信息和单个化合物 这些研究的结果将提供重要的见解， 基于小分子和药物的疫苗设计的一般问题 设计用于调节异常细胞分裂和改变的事件， 恶性细胞特有的凋亡途径。

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.