“A rational search for novel anti-drug therapies.” Year 2 of 4

Dr. Lev proposes a three-pronged research design based on her findings stemming from the previously funded DTRF seed grant that will address these knowledge deficits. Her studies will focus on improving the understanding of the role of ß-catenin, a protein which is highly deregulated in desmoids, on tumor progression and recurrence. Studies will use cell strains and also siRNA screens to identify potential anti-desmoid therapeutic targets. Aim 1: To validate the prognostic impact of the specific beta-catenin 45F mutation in predicting the outcome of patients with primary desmoids. Aim 2: To identify the molecular deregulations contributing to sensitivity or resistance to the commonly used anti-desmoid therapies mainly tamoxifen, NSAIDs (sulindac), and Gleevec. Aim 3: To identify potential novel anti-desmoid therapeutic targets using a rational siRNA screen.