Case GI SPORE

总体总结/摘要 这种情况下GI孢子更新申请提供了一个前沿的专业研究计划 擅长胃肠道恶性肿瘤，重点是结直肠癌和腺癌， 食道这个综合性的项目建立在病例综合癌症中心的资源之上 提出4个转化研究项目，为GI癌症患者带来新的分子进展。一 3个核心资源系列支持这些项目，并建立了强有力的方案基础设施， 消化道癌症的转化研究。我们进一步发展了一个全面的基础设施， 来自整个案例的基础科学和临床研究人员的新发展研究项目 癌症中心利用我们在培养强调翻译的新教师方面的良好记录 我们还制定了一项有针对性的职业提升计划，以进一步推动 并招募到SPORE教师的翻译研究骨干。4个SPORE转化研究项目 构成了治疗胃肠道癌症的新的尖端方法，包括以下研究：i）靶向15-PGDH 结肠癌肿瘤抑制通路用于预测癌症风险、预测对化学预防的反应 与阿司匹林，和新的结肠癌预防和治疗策略的发展（项目1，博士。 Markowitz，Li和Berger）; ii）阐明突变标记的基础和临床意义， 非裔美国人结肠癌（项目2，Willis，Li和Wang博士）; iii）非裔美国人结肠癌的分子标志物的开发 和Barrett食管和早期食管腺癌的非内窥镜检测（项目3，Drs. Chak，Guda和Markowitz）;和iv）开发PIK 3CA突变结肠癌的个性化治疗 使用谷氨酰胺代谢的靶向抑制剂（项目4，王博士和Meropol）。这些项目是建立在 关于SPORE第一个资助期的主要进展，包括：i）在《科学》杂志上发表的15-PGDH 调节结肠隐窝干细胞; ii）在《科学转化医学》上发表的文章， 水平调节服用阿司匹林是否会降低他们的结肠癌风险; iii）在Proceedings上发表 美国国家科学院的基因优先针对结直肠癌的体细胞突变 iv）在《癌症流行病学、生物标志物和预防》的封面上发表文章， 在食管刷检物中检测甲基化波形蛋白DNA可以检测到超过90%的Barrett食管， 食管腺癌; v）在Nature Communications上发表的PIK 3CA突变型癌症是 对谷氨酰胺上瘾，对谷氨酰胺代谢抑制剂敏感。这些项目是由 为评估胃肠道癌症生物标志物开发的特殊人群和科学资源，新药 新发现、福尔马林固定肿瘤样本的下一代测序以及巴雷特食管的研究。 这些调查人员的力量和他们所掌握的资源将确保这一计划产生重大影响。 重要的翻译进展。

OVERALL SUMMARY/ABSTRACT This Case GI SPORE renewal application provides for a cutting edged Specialized Program of Research Excellence in gastrointestinal malignancies with emphasis on colorectal cancers and adenocarcinoma of the esophagus. This comprehensive program builds on the resources of the Case Comprehensive Cancer Center to propose 4 translational Research Projects to bring new molecular advances to patients with GI Cancers. A series of 3 core resources support these projects and also establish a strong programmatic infrastructure for translational research in GI cancers. We have further developed a comprehensive infrastructure for identifying new Developmental Research Projects from basic science and clinical investigators from across the Case Cancer Center. Drawing on our strong track record of developing new faculty who emphasize translational research in GI cancers, we have also developed a targeted Career Enhancement Program to further advance and recruit to the translational research cadre of SPORE faculty. The 4 SPORE translational research projects constitute novel and cutting edge approaches to GI cancers and include studies of: i) Targeting the 15-PGDH colon cancer tumor suppressor pathway for prediction of cancer risk, prediction of response to chemoprevention with aspirin, and development of new colon cancer prevention and treatment strategies (Project 1, Drs. Markowitz, Li, and Berger); ii) Elucidating the basis for and the clinical significance of a mutational signature of African American colon cancer (Project 2, Drs. Willis, Li, and Wang); iii) Development of molecular markers of and non-endoscopic detection of Barrett's esophagus and early esophageal adenocarcinomas (Project 3, Drs. Chak, Guda, and Markowitz); and iv) Development of personalized treatment of PIK3CA mutant colon cancers using targeted inhibitors of glutamine metabolism (Project 4, Drs. Wang and Meropol). These projects are built on major advances from the SPORE's first funding period that include: i) publication in Science that 15-PGDH regulates colon crypt stem cells; ii) publication in Science Translational Medicine that individual's 15-PGDH levels regulate whether taking aspirin will or will not reduce their colon cancer risk; iii) publication in Proceedings of the National Academy of Sciences of genes preferentially targeted for somatic mutations in colorectal cancers of African Americans; iv) publication on the cover of Cancer Epidemiology, Biomarkers and Prevention that testing for methylated vimentin DNA in esophageal brushings could detect over 90% of Barrett's esophagus and esophageal adenocarcinomas; v) publication in Nature Communications that PIK3CA mutant cancers are addicted to glutamine and sensitive to inhibitors of glutamine metabolism. These projects are advantaged by special populations and scientific resources developed for evaluation of GI cancer biomarkers, new drug discovery, Next-Generation sequencing of formalin fixed tumor samples, and studies of Barrett's esophagus. The strength of these investigators and the resources at their disposal will insure this program leads to significant important translational advances.