Specialized Program Research Excellence (SPORE) in Gastrointestinal Cancer

描述（由申请人提供）：2006年，在美利坚合众国，胃肠道（GI）癌症占癌症死亡的近20%，并且结肠直肠癌（CRC）仍然是这种死亡的第二大原因。我们在GI癌症中的SPORE的长期目标是通过开发用于风险评估、筛查、化学预防和治疗的新方法来降低GI癌症导致的死亡率。提出了四个项目，三个核心和发展性研究和职业发展计划。项目1的题目是遗传变异作为结直肠上皮内瘤变（IEN）的预后或预测因素。该项目的转化目标是证明，根据宿主和腺瘤特征，在高危人群中进行量身定制的预防治疗，将减少具有临床意义的结肠肠内营养的发展。项目2的题目是结肠造影在结直肠癌筛查中的应用和发展。该项目的翻译目标是将联合收割机最小口腔清洁肠道准备与病变特异性靶向药物结合，以检测无症状受试者的大息肉和早期癌症。项目3的题目是胃肠道癌应激反应的机制转化研究。该项目的转化目标是利用与肿瘤中改变的血液灌注相关的过程以获得治疗益处。项目4的标题为药物靶向c-MYC启动子中的G-Quadraplex-NM 23-H2复合物，并靶向GI癌症发展中的重要癌基因。项目3和4的转化目标都是开发用于治疗GI癌症的新型靶向药物。这些项目由广泛的人类胃肠道组织资源支持，其包括获取现有的正常和肿瘤组织样本，包括血液、尿液和粪便样本的子集，这些样本是从结肠息肉预防试验中的大约6000名参与者、超过600名患有巴雷特食管的患者和超过500名接受各种胃肠道恶性肿瘤治疗的手术患者收集的。统计和信息学核心将为我们努力发现新的预后标志物和药物靶点的所有项目提供最先进的统计，计算和信息学支持。评估和管理核心是生产性SPORE所必需的关键反馈回路。发展研究计划将确保最有前途的翻译想法得到培育和资助。补充职业发展计划将支持和指导医生和科学家在转化研究。这一竞争性更新申请建立在上一个资助期取得的成功基础上，包括开发几种新的靶向癌症疗法，并利用亚利桑那大学的资源。安德森癌症中心和翻译基因组学研究所（TGEN）提供独特的机会，以实现我们的目标，降低死亡率由于胃肠道癌症在美国。

DESCRIPTION (provided by applicant): Gastrointestinal (Gl) cancers account for nearly 20 percent of cancer deaths in the United States of America in 2006 and colorectal cancer (CRC) continues to be the second leading cause of such deaths. The long-term objective of our SPORE in Gl Cancers is to decrease mortality due to Gl cancers by developing novel approaches for risk assessment, screening, chemoprevention and therapeutics. Four projects, three cores and developmental research and career development programs are proposed. Project 1 is entitled Genetic Variability as Prognostic or Predictive Factors in Colorectal Intraepithelial Neoplasia (IEN). The translational goal of this project is to demonstrate that tailoring prevention therapy in high-risk individuals, based on host and adenoma characteristics, will reduce the development of clinically significant colonic IEN. Project 2 is entitled Application and Development of Colonography for Colorectal Cancer Screening. The translational goal of this project is to combine minimal oral cleansing bowel preparation with lesion-specific targeting agents to detect large polyps and early cancers in asymptomatic subjects. Project 3 is entitled Mechanistic Translational Studies of the Stress Response in Gastrointestinal Cancer. The translational goal of this project is to exploit processes associated with altered blood perfusion in tumors for therapeutic benefit. Project 4 is entitled Drug Targeting of G-Quadraplex-NM23-H2 Complex in the c-MYC Promoter, and targets an important oncogene in Gl cancer development. The translational goal of both Projects 3 and 4 are to develop novel target-directed drugs for treatment of Gl cancers. The projects are supported by an extensive Human Gl Tissue Resource, which includes access to existing normal and neoplastic tissue specimens, including a subset of blood, urine and fecal samples, which have been gathered from approximately 6000 participants in colon polyp prevention trials, over 600 patients with Barrett's esophagus, and over 500 surgical patients who were treated for various Gl malignancies. A Statistical and Informatics Core will provide state-of-the-art statistical, computational and informatics support for all projects in our efforts to discover new prognostic markers and drug targets. The Evaluation and Administration Core is the critical feedback loop necessary for a productive SPORE. The Developmental Research Program will ensure that the most promising translational ideas are nurtured and funded. The complementary Career Development Program will support and mentor physicians and scientists in translational research. This competing renewal application builds on successes achieved during the previous funding period, including the development of several new target directed cancer therapies, and leverages resources at The University of Arizona, M.D. Anderson Cancer Center and the Translational Genomics Research Institute (TGEN) to offer unique opportunities to achieve our goal of reducing mortality due to Gl cancers in the United States.