Program 32: Gastrointestinal Malignancies

胃肠道恶性肿瘤项目 项目总结/摘要 胃肠道恶性肿瘤项目的首要目标是预防，早期发现和管理 更准确有效地治疗胃肠道恶性肿瘤，同时解决与健康相关的关键问题 差距。该计划将应用尖端的基因组技术，以确定遗传和表观遗传 这些变化在GI癌症的发生和进展以及对治疗的反应中很重要。 分子和基因组生物标志物的发现和应用，部分通过无细胞生物标志物的进展来确定。 DNA技术是一个重要的焦点。该计划的范围涵盖一系列癌症： 食管、胃、胰腺、肝胆和结肠直肠。这些癌症中的许多不成比例地 在我们的集水区（马萨诸塞州）或历史上处于不利地位的人群中， 因此，DF/HCC已将这些癌症指定为该中心的高度优先事项。 该方案的112名成员（82名小学生和30名中学生）代表了所有7个联邦区/高等教育委员会机构， 学术部门。2019年，该计划的同行评审赠款为440万美元， NCI的直接费用和其他赞助商的700万美元。在本财政期间，主要 项目成员发表了1,461篇与癌症相关的论文。其中，24%是机构间的，23%是 43%是两个或两个以上DF/HCC成员之间的计划内合作。 这些数字反映了癌症中心对战略愿景指导下的合作研究的重视。 在下一个CCSG发现期，该计划的5个具体目标是：1）利用基因组规模分析 以及实验室和患者衍生模型，以识别新的分子脆弱性和精确肿瘤学 胃肠道恶性肿瘤的战略; 2）支持新兴技术和合作翻译努力， 确定肿瘤异质性的影响和对GI癌症靶向治疗耐药的机制; 3） 定义GI癌症中的肿瘤微环境，并确定对以下药物的反应或耐药的关键机制： 4）设计和执行新型靶向治疗和免疫治疗临床试验， 胃肠道恶性肿瘤的相关研究;和5）开发早期癌症检测方法和早期癌症 针对GI癌症的干预性临床试验跨越多个人群，特别是服务不足的社区。到 为了实现这些目标，我们将充分利用DF/HCC的协作基础设施、核心设施、临床 试验设备，以及社区参与和癌症研究培训的结构化过程。

Gastrointestinal Malignancies Program Project Summary / Abstract The overarching goals of the Gastrointestinal Malignancies Program are to prevent, detect early, and manage more accurately and effectively the treatment of GI malignancies, while addressing key issues related to health disparities. The Program will apply cutting-edge genomic technologies to identify genetic and epigenetic changes that are important in initiation and progression of GI cancers, as well as their response to therapy. Discovery and application of molecular and genomic biomarkers, identified in part through advances in cell-free DNA technologies, represent one important focus. The Program’s scope extends across a range of cancers: esophageal, gastric, pancreatic, hepatobiliary, and colorectal. Many of these cancers have disproportionately high burdens or incidence in our catchment area (Massachusetts) or among historically disadvantaged populations; accordingly, DF/HCC has designated these cancers as a high priority for the Center to tackle. The Program’s 112 members (82 primary and 30 secondary) represent all seven DF/HCC institutions and 14 academic departments. In 2019, peer-reviewed grant funding attributed to the Program was $4.4 million in direct costs from the NCI and $7.0 million from other sponsors. During the current funding period, primary Program members published 1,461 cancer-relevant papers. Of these, 24% were inter-institutional, 23% were intra-programmatic, and 43% were inter-programmatic collaborations between two or more DF/HCC members. These numbers reflect the Cancer Center’s emphasis on collaborative research guided by a strategic vision. For the next CCSG finding period, the Program’s 5 specific aims are to : 1) Leverage genome-scale analyses and laboratory and patient-derived models to identify novel molecular vulnerabilities and precision oncology strategies in GI malignancies; 2) Harness emerging technologies and collaborative translational efforts to define the impact of tumor heterogeneity and mechanisms of resistance to targeted therapies in GI cancers; 3) Define the tumor microenvironment in GI cancers and identify key mechanisms of response or resistance to immunotherapies; 4) Design and execute novel targeted therapy and immunotherapy clinical trials and key correlative studies for GI malignancies; and 5) Develop early cancer detection approaches and early cancer intervention clinical trials for GI cancers cross multiple populations, especially underserved communities. To execute these Aims, we will take full advantage of DF/HCC’s collaborative infrastructure, core facilities, clinical trials apparatus, and structured processes for community engagement and cancer research training.