Colon Cancer Chemoprevention by Balsalazide & Metabolite

Colon cancer is the second leading cause of death due to malignancy in the U.S. Currenttreatments have failed to increase a poor five year survival rate of less than 50%. A safe and effectivepreventative therapy administered to patients at risk of developing colon cancer is needed. Thesestudies will examine the efficacy of a potential chemopreventive agent for colon cancer which hasshown promising activity on aberrant crypt development and colon cancer cell proliferation. Recentevidence has shown this class of compounds, the non-steroid anti inflammatory drugs (NSAIDs) to inhibitcolon tumor incidence in carcinogen induced animal models and inhibit polyp growth in humans.However, most NSAID compounds have serious and sometimes life threatening gastrointestinal sideeffects which preclude their chronic use. The drug substance, balsalazide sodium, is a colonic-specific,NSAI aminosaliclate currently undergoing multi-center Phase III trials for the treatment of activeulcerative colitis. These studies will examine, in a rat model, the efficacy of balsalazide and itsmetabolites on carcinogen-induced development of aberrant colonic crypts as a pre-cancerous lesion.Additional studies will correlate growth inhibition of colon cancer cells in culture by balsalazide, withexpression of two biomarker gene products, secretory phospholipase A2 (PLA2) and the urokinaseplasminogen activator receptor (uPAR) whose expression convey an invasive phenotype to the coloncancer cell. The results will be the basis for designing the Phase II studies which will test thechemopreventive activity of balsalazide in human trials.