UCI 07-70: INHIBITING EGF RECEPTOR SIGNALING IN ABERRANT CRYPT FOCI OF THE COLON

UCI 07-70：抑制结肠异常隐窝灶中的 EGF 受体信号传导

• 批准号: 8166931
• 负责人: Steven M Lipkin
• 金额: $ 0.09万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166931
• 关键词: Aberrant crypt foci; Adverse effects; Cancer Etiology; Cancer Model; Cardiovascular system; Cessation of life; Colon; Colonoscopy; Colorectal; Colorectal Cancer; Computer Retrieval of Information on Scientific Projects Database; EGFR inhibition; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Epithelium; Funding; Gefitinib; Grant; Head and Neck Cancer; Institution; Malignant Neoplasms; Mus; New Agents; Non-Small-Cell Lung Carcinoma; Non-Steroidal Anti-Inflammatory Agents; PTGS2 gene; Pancreas; Play; Premalignant; Prevention; Rattus; Receptor Signaling; Research; Research Personnel; Resources; Role; Screening procedure; Source; Uncertainty; United States; United States National Institutes of Health; adenoma; cancer initiation; inhibitor/antagonist; interest; prevent; small molecule; tumor; tumor initiation; tumor progression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Colorectal cancer (CRC) is the 2nd leading cause of cancer death in the United States. Tragically, a large proportion of CRC is preventable because the tumors are relatively slow growing and we have the ability to detect cancers early with colonoscopy. Most CRC cases are preceded by precursor adenomas, and recent decreases in CRC in the US are attributable to increased screening of adenomas. There has therefore been intensive interest in preventing CRC by targeting precancerous CRC precursors in colorectal epithelium. NSAIDs and COX-2 inhibitors have shown activity in adenoma prevention; however, cardiovascular side effects have created uncertainty as to their suitability for this indication. Therefore, new agents are needed. EGFR inhibition has significant activity to shrink tumors and extend survival in colorectal cancer (CRC), non-small cell lung cancer, pancreas and head and neck cancers. While most of the focus on EGFR inhibitors has been in the treatment of advanced malignancies, there is significant evidence that EGFR also plays important roles in CRC initiation, and that EGFR inhibitors block tumor initiation. In ApcMin mice, EGFR inactivation essentially abolishes adenoma formation. Similarly, treatment of mouse and rat CRC models with the EGFR small molecule inhibitor Gefitinib also blocks adenoma formation. Therefore, it is likely that EGFR plays a role in initiation of adenomas, in addition to its more intensively studied role in tumor progression.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 结直肠癌（CRC）是美国癌症死亡的第二大原因。可悲的是，很大一部分结直肠癌是可以预防的，因为肿瘤生长相对缓慢，而且我们有能力通过结肠镜检查早期发现癌症。大多数结直肠癌病例之前都有腺瘤前兆，最近美国结直肠癌病例的减少归因于腺瘤筛查的增加。因此，人们对通过靶向结直肠上皮中的癌前结直肠癌前体来预防结直肠癌产生了浓厚的兴趣。 NSAIDs 和 COX-2 抑制剂已显示出预防腺瘤的活性；然而，心血管副作用造成了其是否适合该适应症的不确定性。因此，需要新的代理。 EGFR 抑制对于缩小结直肠癌 (CRC)、非小细胞肺癌、胰腺癌和头颈癌的肿瘤并延长生存期具有显着的活性。虽然 EGFR 抑制剂的大部分关注点都集中在晚期恶性肿瘤的治疗上，但有大量证据表明 EGFR 在 CRC 中也发挥着重要作用 EGFR 抑制剂阻断肿瘤的发生。在 ApcMin 小鼠中，EGFR 失活基本上消除了腺瘤的形成。同样，用 EGFR 小分子抑制剂吉非替尼治疗小鼠和大鼠 CRC 模型也能阻止腺瘤形成。因此，除了对肿瘤进展中的作用进行更深入的研究外，EGFR 很可能在腺瘤的发生中发挥作用。