Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer

项目摘要 这是一个有竞争力的更新申请的孢子在胃肠道（GI）癌症起源于胃肠道 Dana-Farber/哈佛癌症中心（DF/HCC）的肿瘤项目。自2007年成立以来， SPORE建立了一种蓬勃发展的机构间合作文化，将基础、临床和 将人口科学家转变为一个高效的转化企业。吸引和留住人才的能力 来自不同学科的研究人员促进了癌症生物学的基本发现， 转化假说和尖端临床试验。SPORE还将重点放在 发展一大批新的调查人员，建立在跨学科、跨学科的成功模式的基础上， 校园合作，作为一个nidus为孢子间的关系和其他合作。此外，委员会认为， SPORE创造了宝贵的研究资源，如组织、PDX和类器官库 以及共同加速翻译研究的临床、病理学和基因组学数据库。中的每 目前的项目已经实现或超过了其翻译目标，为方案提供了基础。 研究，包括独立的大规模合作倡议。在此基础上，DF/HCC GI SPORE致力于继续将生物和技术进步转化为 预防和治疗胃肠道恶性肿瘤。 更新后的SPORE的总体目标是：1）定义最佳的基因组和功能策略， 包括整合无细胞（cf）DNA分析（项目1-4），以预测药物反应性并改善 诊断学、病理学和临床决策。2)阐明致癌突变之间的相互作用， 靶向治疗和抗肿瘤免疫，以告知癌症生物学，并改善患者的结果， 胃肠道癌症（项目1、3、4）。3)定义对新型靶向治疗的耐药机制， 确定克服耐药性的新方法，更好地选择最有可能对治疗产生反应的患者 （项目1-4）。4)加强对致命胃肠道癌症的研究，尽管发病率上升，但仍处于... 研究（项目2，4）。5)通过提供临床标本，鼓励合作并促进学术严谨性， 培育核心技术和资源，定期举办以地理信息系统为重点的研究会议和研讨会 癌的6)为年轻的GI癌症研究人员提供指导和培训，并招募领先的翻译人员 通过职业提升和发展项目奖从其他领域的调查员。

Project Summary This is a competitive renewal application for a SPORE in Gastrointestinal (GI) Cancers originating from the GI Malignancies Program of the Dana-Farber/Harvard Cancer Center (DF/HCC). Since its inception in 2007, the SPORE has established a thriving culture of inter-institutional collaboration that has united basic, clinical, and population scientists into a highly productive translational enterprise. The ability to attract and retain researchers from diverse disciplines has fostered fundamental discoveries in cancer biology, innovative translational hypotheses, and cutting-edge clinical trials. The SPORE has also maintained a central focus on developing a large cadre of new investigators, building on a successful model of interdisciplinary, cross- campus cooperation that serves as a nidus for inter-SPORE relationships and other collaborations. Moreover, the SPORE has created invaluable research resources, such as the Tissue, PDX and Organoid Repository and clinical, pathology, and genomics databases that collectively accelerate translational investigation. Each of the current projects has achieved or exceeded its translational goals, providing a foundation for programmatic studies, including independent large-scale collaborative initiatives. Building on this progress, the DF/HCC GI SPORE seeks to continue to translate biological and technological advances into improvements in the prevention and treatment of GI malignancies. The overarching objectives of a renewed SPORE are to: 1) Define optimal genomic and functional strategies, including integration of cell-free (cf)DNA profiling (Projects 1-4), to predict drug responsiveness and improve diagnostics, prognostics, and clinical decisions. 2) Elucidate the interplay between oncogenic mutations, targeted therapy, and anti-tumor immunity to inform cancer biology and improve the outcome of patients with GI cancers (Projects 1,3, 4). 3) Define mechanisms of resistance to novel targeted therapies and hence identify new approaches to overcome resistance and better select the patients most likely to respond to therapy (Projects 1-4). 4) Enhance study of deadly GI cancers that, despite rising incidence, remain under- studied (Project 2, 4). 5) Encourage collaboration and promote academic rigor by providing clinical specimens, fostering core technologies and resources, and hosting regular research meetings and seminars focused on GI cancers. 6) Provide mentorship and training for young GI cancer researchers and recruit leading translational investigators from other fields through Career Enhancement and Developmental Project Awards.