Restoration of Wild-Type Activity to Mutant p53 in Prostate Cancer: A Novel Therapeutic Approach; Final rept. 6 Dec 2004-5 Dec 2007

摘要

A summary is presented of research performed during three years of a project to determine feasibility of approaches to restore wild-type transcriptional activity on mutant p53 proteins found in human prostate tumors. p53 mutant proteins that are specifically relevant to prostate cancer were examined to determine whether they are suitable targets for such an approach. Three specific aims were pursued. The first was characterizing the interaction of p53 with two distinct classes of its response elements. The second aim was determining the role of mutant p53 proteins in prostate cancer cell proliferation. The final aim was to explore approaches to restore wild-type function to mutant p53 proteins found in prostate cancer. The long-term goals of this research were to identify small molecular weight compounds that have the novel activity of restoring wild-type function to prostate cancer-derived mutant p53 proteins. As such, this represented a preclinical development of highly targeted therapy with the hope of establishing highly effective and tumor-specific treatments of human prostate cancer.