MD Anderson Cancer Center SPORE in Gastrointestinal Cancer

MD 安德森癌症中心 SPORE 在胃肠道癌症中的应用

• 批准号: 10415964
• 负责人: Scott Kopetz
• 金额: $ 221.13万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-20 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10415964
• 关键词: Address; Adenocarcinoma; Adjuvant; Advocate; Agonist; Animal Model; Anti-CD40; Archives; Award; Bioinformatics; Biological; Biological Markers; Biometry; Cancer Center; Cancer Etiology; Cessation of life; Chemoprevention; Chronic; Clinic; Clinical; Clinical Research; Clinical Trials; Collaborations; Colonic Adenoma; Colonic inflammation; Colorectal Cancer; Combined Modality Therapy; Combined Vaccines; Communities; Complement; Country; Data; Data Analyses; Dependence; Development; Diagnostic; Disease; Environment; Excision; Failure; Familial Adenomatous Polyposis Syndrome; Familial colorectal cancer; Funding; Future; Genetic Engineering; Goals; Grant; Hereditary Nonpolyposis Colorectal Neoplasms; Image; Immune; Immune checkpoint inhibitor; Immunotherapeutic agent; Inflammation; Inflammatory Bowel Diseases; Inherited; Institution; International; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of pancreas; Mentors; Microsatellite Instability; Minority; Mitochondria; Molecular; Morbidity - disease rate; Mus; Oncogenic; Operative Surgical Procedures; Organoids; Outcome; Oxidative Phosphorylation; Pancreas; Pancreatic Ductal Adenocarcinoma; Pathology; Patients; Peptide Vaccines; Pharmacodynamics; Phase; Pilot Projects; Populations at Risk; Positioning Attribute; Pre-Clinical Model; Prevention; Prevention trial; Pyruvate; Quality of life; Reporting; Research; Research Personnel; Resected; Residual Neoplasm; Residual Tumors; Resistance; Role; STAT3 gene; Sampling; Signal Pathway; Signal Transduction; Stat3 protein; Syndrome; TLR7 gene; Therapeutic; Translating; Translational Research; Ulcerative Colitis; Universities; Vaccination; Vaccine Therapy; Woman; Work; anti-PD-1; anti-tumor immune response; base; cancer immunotherapy; career; chemotherapy; clinical care; colon cancer patients; colorectal cancer risk; colorectal cancer treatment; design; early-career faculty; efficacy testing; first-in-human; high risk; imaging study; improved; inhibitor; innovation; metabolic imaging; metastatic colorectal; mortality; multidisciplinary; neoantigens; novel; novel therapeutics; pancreatic cancer model; patient derived xenograft model; pre-clinical; programs; prospective; radiological imaging; recruit; resistance mechanism; response; standard of care; translational impact; translational scientist; trial design; tumor DNA; tumor metabolism; vaccine trial

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

总体而言：总结/摘要 MD 安德森 SPORE 胃肠癌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 影响这些疾病患者的生活。结直肠癌是癌症相关死亡的第二大常见原因 这个国家，而 PDAC 是第三大最常见的原因，强调了这项工作的重要性 在本提案中进行。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，以便为 CRC 和 PDAC 患者提供进一步的治疗选择。这 GI SPORE 将由 Scott Kopetz 和 Anirban Maitra 共同领导，他们在翻译领域有着丰富的经验 分别是 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结直肠癌切除后患者辅助治疗中的功效，以及 还在临床前模型中评估针对这种疾病的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，代表了我们共同的观点的融合 癌症免疫治疗和免疫相关领域的专业知识。项目2将评估致癌物质的作用 STAT3 信号在慢性炎症相关和遗传性 CRC 中的作用，使用遗传组合 工程动物模型和患者来源的类器官（PDO）。此外，该项目还将开展 使用内部开发的 STAT3 抑制剂进行预防研究。项目 3 将评估生物相关性 对新型氧化抑制剂的反应和耐药性（包括代谢成像研究） PDAC 中的磷酸化 (OXPHOS)，使用我们的大量基因注释的患者来源的库 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，并伴随新颖的成像和 分子相关物。我们计划的一个重要目标是招募女性和少数族裔 通过职业提升计划（CEP）进入现场并指导早期职业教师，以及 通过发展研究计划（DRP）资助创新试点项目。行政 旨在维护财务责任以及报告和机构合规性的核心将支持 所有三个项目。生物样本和病理学核心将支持所有临床和研究生物样本 这三个项目的需求以及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。已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 GI SPORE 团队经过战略性组织，能够有效地翻译 我们的临床前概念和新靶标迅速进入临床环境，目标是对 CRC 和 PDAC 死亡率