The research involves laboratory studies utilizing xenograft models to test the hypothesis that targeting a member of the ETS transcription factor family with small molecules such as YK-4-279 may effectively treat prostate cancer. In year three, Dr. Morrissey was to evaluate the anti-tumor effect of the S-enantiomer of YK-4-279 on 4 human prostate xenograft lines subcutaneously and 2 lines intra-tibial. Dr. Uren supplied Dr. Morrissey with the required compound. The S-enantiomer of YK-4-279 had no significant effect on tumor growth on the first and second ERG xenograft. It had an effect on the third ERG xenograft line, and no effect on the control xenograft line. A gene expression analysis of the first study suggested a change in the expression of epithelial-mesenchymal transition associated genes in ERG treated tumors. However, immunohistochemical analyses of these proteins in the tumors of treated and untreated animals suggested the change in expression only occurred in a subset of cells within the tumors. Dr. Uren has met with and Skyped with Dr. Morrissey to ensure continued collaboration. We are currently completing a study on the effect of the S-enantiomer of YK-4-279 on intra-tibial tumors and have requested a no cost extension to complete the intra-tibial animal studies.