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

IGF::OT::IGF PREVENT 功效任务顺序：用奥美沙坦酯化学预防结直肠癌

• 批准号: 9574580
• 负责人: Chinthalapally Rao
• 金额: $ 52.21万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9574580
• 关键词: Aberrant crypt foci; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Aspirin; Biological Markers; Cancer Etiology; Captopril; Cardiovascular system; Case-Control Studies; Cell Survival; Chemoprevention; Clinic; Colorectal Cancer; Diagnosis; Dose; Drug usage; Generations; Inflammation; PTGS2 gene; Pharmaceutical Preparations; Property; Risk; Safety; Signal Transduction; Toxic effect; cancer type; cell growth; clinical efficacy; colorectal cancer prevention; cyclooxygenase 2; gastrointestinal; hypertension treatment; inhibitor/antagonist; mortality; olmesartan; pre-clinical; prevent; telmisartan

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.

结直肠癌 (CRC) 是美国癌症相关死亡的第二大原因，每年诊断出超过 135 万新病例。尽管阿司匹林和环氧合酶-2 (COX-2) 抑制剂等非甾体抗炎药 (NSAID) 在动物模型和临床中被证明可有效预防结直肠癌，但其使用受到胃肠道和心血管毒性的严重限制。因此，寻找更安全的结直肠癌化学预防剂的需求尚未得到满足。第三代血管紧张素受体阻滞剂（ARB）奥美沙丁酯是美国最常用于治疗高血压的处方药物。 ARB 和血管紧张素转换酶 (ACE) 抑制剂已被证明可以减少炎症并抑制细胞生长和存活，几项回顾性病例对照研究揭示了使用这些药物与降低多种不同类型癌症（包括结直肠癌）风险之间的关联。此外，血管紧张素信号传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。 ARB 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 CRC 化学预防药物的有吸引力的候选者。本任务单的目的是评估奥美沙丁酯用于预防 CRC 的作用。