Genetic Screening:Oncogene RAS-Based Inhibi*(RMI)

基因筛查：Oncogene RAS-Based Inhibi*(RMI)

• 批准号: 7058055
• 负责人: XIAODONG CHENG
• 金额: $ 0.45万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2007-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058055
• 关键词: antineoplastics; biotechnology; cell line; chemical genetics; drug screening /evaluation; guanine nucleotide binding protein; high throughput technology; oncogenes; pancreas neoplasms; technology /technique development

DESCRIPTION (provided by applicant): Pancreatic cancer is one of the most aggressive and devastating human disease. Almost all patients diagnosed with the disease die from the malignancy with a medium survival of less than six months. Clinically, the disease often evades detection during its early stages due to the lack of specific symptoms and limitation in diagnostic methods. Adding to this problem, pancreatic cancer is resistance to most forms of treatments such as chemotherapy, radiation, and combination therapy. One single most important cause for such a dismal clinic prognosis of pancreatic cancer is the lack of fundamental understanding of basic biology of human pancreas both under physiological and pathophysiological conditions. A recent study by the National Cancer Institute Pancreatic Cancer Progress Review Group concluded that pancreatic cancer is disproportionately underrepresented in both clinical and basic research compared with other cancer sites. Although many of the genetic changes associated with pancreatic cancer development have been revealed, significant gaps exist in our understanding of how these genetic alterations lead to the initiation, development, and maintenance of pancreatic cancer. This information is essential for develop new and effective diagnostics and treatments for pancreatic cancer. One major roadblock for pancreatic cancer research is the lack of genetically tractable human cancer cell model systems to investigate the origins and progression of pancreatic cancer. To overcome this barrier, we have recently developed a genetically defined human pancreatic cancer cell model using genetic components known to be frequently altered in pancreatic cancer. We will use our genetically defined human pancreatic cancer model to screen chemical libraries for the purpose of discovering of chemical compounds that preferentially kill the cancer cells but not normal human pancreatic cells. These studies may lead to the identification of potential novel and effective treatments for pancreatic cancer. In addition, the identification of such mechanism-based chemical inhibitors will also aid the elucidation of down-stream signaling pathways of these well-defined genetic alterations that are important for the initiation and development of this destructive disease.

描述（由申请人提供）：胰腺癌是最具侵略性和毁灭性的人类疾病之一。几乎所有被诊断出患有这种疾病的患者死于恶性肿瘤，中等生存期少于六个月。在临床上，由于缺乏特定症状和诊断方法的限制，该疾病经常在早期阶段逃避检测。除此问题外，胰腺癌是对大多数疗法的抗性，例如化学疗法，放射和联合疗法。这种令人沮丧的胰腺癌诊所预后的最重要原因是在生理和病理生理条件下对人类胰腺的基本生物学缺乏基本了解。国家癌症研究所胰腺癌进度评论小组最近的一项研究得出结论，与其他癌症部位相比，胰腺癌在临床和基础研究中的比例不足。尽管已经揭示了许多与胰腺癌发展相关的遗传变化，但我们对这些遗传改变如何导致胰腺癌的起始，发育和维持的理解存在很大的差距。此信息对于开发新的有效诊断和治疗胰腺癌至关重要。胰腺癌研究的一个主要障碍是缺乏可研究胰腺癌的起源和进展的遗传学疗法的人类癌细胞模型系统。为了克服这一障碍，我们最近使用已知在胰腺癌中经常改变的遗传成分开发了一种遗传定义的人胰腺癌细胞模型。我们将使用遗传定义的人类胰腺癌模型来筛选化学文库，以发现优先杀死癌细胞但不是正常人类胰腺细胞的化学化合物。这些研究可能导致鉴定潜在的新型和有效治疗胰腺癌。此外，对这种基于机制的化学抑制剂的鉴定还将有助于阐明这些明确定义的遗传改变的下游信号传导途径，这对于这种破坏性疾病的启动和发展很重要。