Colon cancer is the second leading cause of death due to malignancy in the U.S. Current treatments have failed .to increase a poor five year survival rate of less than 50%. A safe and effective preventative therapy administered to patients at risk of developing colon cancer is needed. These studies will examine the efficacy of a potential chemopreventive agent for colon cancer which has shown promising activity on aberrant crypt development and colon cancer cell proliferation. Recent evidence has shown this class of compounds, the non steroid anti inflammatory drugs (NSAIDs) to inhibit colon tumor incidence in carcinogen induced animal models and inhibit polyp growth in humans. However, most NSAID compounds have serious and sometimes life threatening gastrointestinal side effects 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 active ulcerative colitis. These studies will examine, in a rat model, the efficacy of balsalazide and its metabolites on carcinogen induced development of aberrant coloni Phase I Grants crypts as a pre cancerous lesion. Additional studies will correlate growth inhibition of colon cancer cells in culture by balsalazide, with expression of two biomarker gene products, secretory phospholipase A2 (PLA2) and the urokinase plasminozen activator receptor (uPAR) whose expression conveY an invasive phenotype to the colon cancer cell. The results wNl be the basis for designing the Phase 11 studies which will test the chemopreventive activity of balsalazide in human trials.Commercial ApplicationsPositive results from the proposed studies will allow testing of balsalazide in humans for chemoprevention of colon cancer. As balsalazlde is an exceptionally well tolerated drug, it could be used for chronic and prophylactic chemoprevention to inhibit colonic polyp progression to the malignant phenotype. There is currently no therapeutic agent with this same potential efficacy and safety profile for this disease.National Cancer Institute (NCI)
