During this past fiscal year, we identified the N-CoR pathway as a regulator of tumor stem cell differentiation and reported pharmacologic ways to manipulate this pathway and inhibit tumor cell growth. We also continued our analysis of the microarray dataset that was initially reported in Lee et al., Cancer Cell (2006)9:391-403. This dataset contains gene expression data for freshly resected tumors and tumor stem cells derived from these tumors, both before and after differentiation. Analysis of the gene expression profiles revealed a number of specific intracellular signalling pathways that may be involved in the differentiation process of tumor stem cells. We will determine the importance of these pathways to tumorigenesis both in vitro and in vivo. Genetic and pharmacologic methods to disrupt the pathways relevant to tumor growth and spread will be explored.