IGF::OT::IGF PREVENT Efficacy Task Order: Chemoprevention of Colorectal Cancer with Olmesartan Medoxomil

结直肠癌(CRC)是美国癌症相关死亡的第二大原因，每年有超过135万新诊断病例。非甾体抗炎药(NSAIDs)如阿司匹林和环氧合酶-2(COX-2)抑制剂在动物模型和临床上被证明是预防结直肠癌的有效药物，但其应用受到胃肠道和心血管毒性的严重限制。因此，寻找更安全的治疗结直肠癌的化学预防药物的需求尚未得到满足。第三代血管紧张素受体阻滞剂(ARB)OlMesartin Medoxomil是美国治疗高血压最常用的处方药。ARBS和血管紧张素转换酶(ACE)抑制剂已被证明可以减少炎症，抑制细胞生长和存活，几项回溯性病例对照研究显示，使用这些药物与降低几种不同类型癌症(包括结直肠癌)的风险之间存在关联。此外，血管紧张素信号转导抑制剂卡托普利和替米沙坦已被证明可以抑制结直肠癌动物模型中结肠异常隐窝病灶的形成。ARBS和ACE抑制剂已知的安全性、心血管保护特性和临床前疗效使它们成为结直肠癌化学预防药物的有吸引力的候选药物。本任务令的目的是评价奥美沙坦用于预防结直肠癌的疗效。

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.