This is the final year of a study started by Dina Lev, MD, Phd at MD Anderson Cancer Center.
The goal is to investigate the molecular driving forces behind the development and progression of desmoid tumors. Dr. Pollock, et al, are trying to identify potential targets that modify beta-catenin transcriptional activity using an siRNA screen. Identifying genes and their cognate proteins whose alteration would inhibit beta-catenin activity might provide future targets for novel molecular therapies relevant to DT patients.
Aim 1: To validate previous findings of the prognostic power of beta-catenin 45F mutation in predicting the outcome of patients with primary desmoids.
Aim 2: To identify the molecular deregulations contributing to the sensitivity or resistance to the commonly used anti-desmoid therapies, mainly Tamoxifen, NSAIDS and Gleevec.
Aim 3: To identify potential novel anti-desmoid therapeutic targets using a rational siRNA screen. Potentially these targets harbor the capacity to modify the transcriptional effect of beta-catenin.
Note: Dr. Lev has previously identified significant associations between the presence of 45F mutations and an increased rate of desmoid recurrence as well as shorter time intervals to recurrence. Analysis of a large primary desmoid subset showed that desmoids having a 45 F mutation had an estimated five year recurrence -free survival rate of only 47% and a median time to recurrence of 3.16 years. In sharp contrast, the estimated five year recurrence free survival rate for all other desmoid primary tumors was 83%; median time to recurrence not yet being reached.
