MD Anderson Cancer Center SPORE in Gastrointestinal Cancer

总体：摘要/摘要 MD安德森SPORE在胃肠道癌症方面的总体目标是降低死亡率和发病率 结直肠癌（CRC）和胰腺导管腺癌（PDAC）的发病率，并提高质量 这些疾病患者的生活。CRC是癌症相关死亡的第二大常见原因， 这个国家，而PDAC是第三个最常见的原因，强调了工作的重要性 在这项提案中。我们的多学科团队将进行高度创新的转化研究 包括首次人体试验，以进一步为CRC和PDAC患者提供治疗选择。的 GI SPORE将由Scott Kopetz和Anirban Maitra共同领导，他们完成了翻译 CRC和PDAC的研究人员。我们提出以下三个项目：项目1将测试 新型个性化肽疫苗在切除术后CRC患者中的佐剂环境中的功效，以及 还在临床前模型中评估用于该疾病疫苗接种的最佳组合疗法。 项目1将与约翰霍普金斯大学合作，代表我们共同的 癌症免疫治疗和免疫相关物的专业知识。项目2将评估致癌基因的作用， STAT 3信号在慢性炎症相关和遗传性结直肠癌中的作用， 工程动物模型和患者衍生的类器官（PDO）。此外，该项目还将开展一项 使用内部开发的STAT 3抑制剂进行预防研究。项目3将评估生物相关性 对一种新型氧化抑制剂的反应和抗性（包括代谢成像研究） PDAC中的磷酸化（OXPHOS），使用我们大量的基因注释的患者来源的 异种移植物（PDX）。此外，我们将在两项临床试验中评估这种OXPHOS抑制剂IACS-10759 分别针对转移性和局部晚期PDAC患者，伴随新型成像， 分子相关物我们计划的一个重要目标是招募妇女和少数民族 通过职业提升计划（CEP）对早期职业教师进行现场指导，以及 通过发展研究计划（DRP）资助创新试点项目。行政 旨在保持财务责任沿着报告和机构合规的核心将支持 这三个项目。生物标本和病理学核心将支持所有临床和研究生物标本 三个项目的需求和生物统计学和生物信息学核心将为试验设计提供支持 和生物统计学。建立的工作关系在许多方面都非常富有成效， 良好定位的团队方法。我们的整个GI SPORE团队是战略性组织，以有效地翻译 我们的临床前概念和新目标迅速进入临床环境，目标是对 CRC和PDAC的死亡率

OVERALL: Summary/Abstract The overall goal of the MD Anderson SPORE in Gastrointestinal Cancer is to reduce mortality and morbidity rates from colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC), and to improve the quality of life of patients afflicted by these diseases. CRC is the 2nd most common cause of cancer-related deaths in this country, while PDAC is the 3rd most common cause, underscoring the significance of the work undertaken in this proposal. Our multidisciplinary team will conduct highly innovative translational research including first-in-human trials in order to further therapeutic options available to CRC and PDAC patients. The GI SPORE will be jointly led by Scott Kopetz and Anirban Maitra, who are accomplished translational researchers in CRC and PDAC, respectively. We propose the following three projects: Project 1 will test the efficacy of a novel personalized peptide vaccine in the adjuvant setting in post-resection CRC patients, and also evaluate in preclinical models the most optimal combination therapies for vaccination in this disease. Project 1 will be a collaboration with Johns Hopkins University, and represents the confluence of our shared expertise in cancer immunotherapy and immune correlatives. Project 2 will evaluate the role of oncogenic STAT3 signaling in chronic inflammation-associated and hereditary CRC, using a combination of genetically engineered animal models and patient-derived organoids (PDOs). In addition, this project will conduct a prevention study with an internally-developed STAT3 inhibitor. Project 3 will evaluate biological correlates of response and resistance (including metabolic imaging studies) to a novel inhibitor of oxidative phosphorylation (OXPHOS) in PDAC, using our substantial repertoire of genetically annotated patient-derived xenografts (PDXs). Further, we will evaluate this OXPHOS inhibitor, IACS-10759, in two clinical trials targeting metastatic and locally advanced PDAC patients, respectively, with accompanying novel imaging and molecular correlatives. An important objective of our program will be the recruiting of women and minorities to the field and mentoring of early career faculty through the Career Enhancement Program (CEP), and funding of innovative pilot projects through the Developmental Research Program (DRP). An Administrative Core designed to maintain fiscal responsibility along with reporting and institutional compliance will support all three projects. A Biospecimen and Pathology Core will support all clinical and research biospecimen needs for the three projects and a Biostatistics and Bioinformatics Core will provide support for trial design and biostatistics. Established working relationships have been extremely productive on many fronts from a well-positioned team approach. Our overall GI SPORE team is strategically organized to effectively translate our preclinical concepts and novel targets rapidly into a clinical setting, with the goal of significant impact on mortality rates from CRC and PDAC