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：摘要/摘要 MD安德森孢子治疗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)的发生率，并提高质量 受这些疾病折磨的患者的生活。结直肠癌是与癌症相关的死亡的第二大常见原因 这个国家，而PDAC是第三个最常见的事业，强调了这项工作的重要性 在本提案中承担的责任。我们的多学科团队将进行高度创新的翻译研究 包括首个人体试验，以进一步为结直肠癌和PDAC患者提供治疗选择。这个 GI孢子将由Scott Kopetz和Anirban Maitra共同领导，他们是熟练的翻译人员 分别在CRC和PDAC的研究人员。我们提出了以下三个项目：项目1将测试 一种新的个性化多肽疫苗在结直肠癌切除术后辅助环境中的疗效 也要在临床前模型中评估在这种疾病中接种疫苗的最佳组合疗法。 项目1将是与约翰·霍普金斯大学的合作，代表着我们共享的 在癌症免疫治疗和免疫相关方面的专业知识。项目2将评估致癌基因的作用 STAT3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有机化合物(PDO)。此外，该项目还将进行一次 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 对一种新型氧化抑制剂的反应和抵抗力(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患者来源的谱系 异种移植(PDX)。此外，我们将在两个临床试验中评估这种氧磷酶抑制剂iacs-10759 分别以转移性和局部晚期PDAC患者为靶点，伴随着新的成像和 分子相关性。我们方案的一个重要目标将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实地和指导，以及 通过发展研究计划(DRP)为创新试点项目提供资金。A管理人员 旨在保持财政责任以及报告和机构合规性的核心将支持 这三个项目都是。一个生物医学和病理学核心将支持所有临床和研究生物医学 三个项目的需求和一个生物统计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，从 定位良好的团队方法。我们的整个GI孢子团队都经过了战略性的组织，以有效地翻译 我们的临床前概念和新目标迅速转化为临床环境，目标是对 结直肠癌和PDAC的死亡率