Specialized Program Research Excellence (SPORE) in Gastrointestinal Cancer

2006年，胃肠道(Gl)癌症占美国癌症死亡的近20%，结直肠癌(CRC)仍然是此类死亡的第二大原因。我们治疗Gl癌的孢子的长期目标是通过开发风险评估、筛查、化学预防和治疗的新方法来降低Gl癌的死亡率。提出了四个项目、三个核心以及发展研究和职业发展计划。项目1题为“作为结肠上皮内瘤变(IEN)的预测或预测因素的遗传变异性”。这个项目的翻译目标是证明，根据宿主和腺瘤的特征，对高危个体进行量身定制的预防治疗将减少临床上有意义的结肠瘤的发生。项目2题为结肠造影术在结直肠癌筛查中的应用和发展。该项目的翻译目标是将最少的口腔清洁肠道准备与病变特异性靶向试剂相结合，以检测无症状受试者的大息肉和早期癌症。项目3名为“胃肠癌应激反应的机制翻译研究”。该项目的翻译目标是利用与肿瘤血液灌流改变相关的过程来获得治疗益处。项目4名为C-MYC启动子中G-四链-NM23-H2复合体的药物靶向，目标是G1癌症发展中的一个重要癌基因。项目3和项目4的翻译目标都是开发治疗Gl癌的新型靶向药物。这些项目得到了广泛的人类Gl组织资源的支持，其中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，这些样本来自大约6000名结肠息肉预防试验参与者、600多名Barrett‘s食道患者和500多名接受过各种Gl恶性肿瘤治疗的外科患者。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标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孢子所必需的关键反馈回路。发展研究计划将确保最有希望的翻译想法得到培育和资助。补充职业发展计划将在翻译研究方面支持和指导医生和科学家。这一竞争性的续签申请建立在上一次资助期间取得的成功的基础上，包括几种新的靶向癌症疗法的开发，并利用亚利桑那大学、M.D.安德森癌症中心和翻译基因组研究所(TGen)的资源，提供独特的机会，以实现我们降低美国G1癌症死亡率的目标。

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.