Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the US, with more than 1.35 million new cases diagnosed each year. Although non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and cyclooxygenase-2 (COX-2) inhibitors were shown to be effective in preventing CRC in animal models and in the clinic, their use is severely limited by gastrointestinal and cardiovascular toxicities. Thus, there is an unmet need for the identification of safer chemopreventative agents for CRC. The third-generation angiotensin receptor blocker (ARB) Olmesartin Medoxomil is the most commonly prescribed medication in the US for the treatment of hypertension. ARBs and angiotensin converting enzyme (ACE) inhibitors have been shown to reduce inflammation and inhibit cell growth and survival, and several retrospective case-control studies have revealed an association between the use of these drugs and a reduced risk for several different types of cancer, including CRC. In addition, the angiotensin signaling inhibitors, Captopril and Telmisartan, have been shown to suppress the formation of colonic aberrant crypt foci in animal models of CRC. The known safety profiles, cardiovascular protective properties, and pre-clinical efficacy of ARBs and ACE inhibitors make them attractive candidates for CRC chemopreventative agents. The purpose of this Task Order is to evaluate Olmesartin Medoxomil for CRC prevention.
