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

基本信息

批准号：
10226083
负责人：
Scott Kopetz
金额：
$ 198.74万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
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/10226083
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 Colorectal Cancer Combined Modality Therapy Combined Vaccines Communities Complement Country Data Data Analyses Dependence Development Diagnostic Diagnostic radiologic examination 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/antagonist innovation metabolic imaging metastatic colorectal mortality multidisciplinary neoantigens novel novel therapeutics pancreatic cancer model patient derived xenograft model pre-clinical programs prospective recruit resistance mechanism response standard of care translational impact translational scientist trial design tumor DNA tumor metabolism vaccine trial

项目摘要

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：摘要/摘要 MD Anderson孢子在胃肠癌中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）的率，并提高质量这些疾病困扰的患者的生命。 CRC是与癌症相关死亡的第二个最常见原因这个国家，虽然PDAC是第三最常见的原因，但强调了工作的重要性在此提案中进行。我们的多学科团队将进行高度创新的翻译研究包括首次人类试验，以进一步可为CRC和PDAC患者提供治疗方案。这 GI Spore将由Scott Kopetz和Anirban Maitra共同领导，他们的翻译成就 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后CRC患者中的辅助设置中的功效，同样在临床前模型中评估该疾病中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，代表我们共享的融合癌症免疫疗法和免疫相关性的专业知识。项目2将评估致癌的作用慢性炎症相关和遗传性CRC中的STAT3信号传导，结合了遗传学工程动物模型和患者衍生的器官（PDOS）。此外，该项目将进行通过内部发达的STAT3抑制剂进行预防研究。项目3将评估生物学相关性对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），使用我们的大量基因注释的患者衍生的曲目异种移植物（PDXS）。此外，我们将在两项临床试验中评估该OXPHOS抑制剂IACS-10759 分别靶向转移性和局部晚期PDAC患者，并随附新型成像和分子相关性。我们计划的重要目标是招募妇女和少数民族通过职业增强计划（CEP）和早期职业教师的领域和指导通过发展研究计划（DRP）为创新的试点项目提供资金。行政旨在维持财政责任以及报告和机构合规性的核心将支持这三个项目。生物测量和病理学核心将支持所有临床和研究生物测试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。建立的工作关系在许多方面都非常有生产力位置良好的团队方法。我们的整体胃肠道孢子团队在战略上组织起来有效地翻译我们的临床前概念和新颖的目标迅速进入临床环境，目的是对 CRC和PDAC的死亡率