Deconvolution and interruption of the cancer-neuro-immune axis facilitating brain metastases

癌症-神经-免疫轴的解卷积和中断促进脑转移

基本信息

批准号：
10706491
负责人：
Melanie Hayden Gephart
金额：
$ 147.68万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-21 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10706491
关键词：
Address Advocate Biology Brain Brain Neoplasms CRISPR library Cancer Patient Clinical Clinical Trials Communication Communities Data Dedications Deterioration Development Diagnostic Disease model Ensure Exclusion Experimental Models Foundations Goals Human Immune system Immunotherapy In Vitro Incidence Interruption Malignant Neoplasms Mediator Metastatic malignant neoplasm to brain Methods Microglia Modeling Molecular Mus Neoplasm Metastasis Neuroimmune Neurologic Office of Administrative Management Organoids Patient risk Patients Physicians Primary Neoplasm Production Productivity Quality of life Research Sampling Scientist Site Specimen Technology Testing Therapeutic Translating Translations Tropism Tumor Tissue Work brain cell data management design experience glycoproteomics high throughput screening human disease human tissue improved in vivo Model innovation insight interest multidisciplinary neoplastic cell neuropathology new therapeutic target novel organizational structure programs synergism therapy resistant tool tumor tumor microenvironment

项目摘要

1 ABSTRACT – OVERALL COMPONENT 2 3 The development of brain metastases, experienced by up to 40% of cancer patients, marks a clear inflection 4 point in survival and quality of life. The inaccessibility of brain tumor tissue has stymied progress in our 5 understanding and treatment of brain metastases, and patients are regularly excluded from clinical trials. The 6 Stanford Brain Metastasis Consortium has unified brain and cancer experts in the singular goal of improving our 7 understanding and treatment of brain metastases, a currently increasing yet underserved subset of cancer 8 patients. To accomplish the above goal, we have: (1) designed an organizational structure that supports 9 scientists in our integrated work; (2) developed highly innovative and complementary Projects to understand 10 and disrupt the cancer-neuro-immune axis supporting brain metastases; and (3) created NeuroPathology 11 and ToolKit Cores to make human specimens and cutting-edge technologies readily accessible to participating 12 scientists. We expect to identify and target key mediators of brain metastasis, with therapeutic benefit for 13 patients. 14 Little is known about the distinct mechanisms that drive tumor cells to the brain and allow them to grow in this 15 unique microenvironment, supported in part by normal brain cells. Streamlined access to human brain 16 specimens, combined with innovations in modeling and manipulation of the tumor microenvironment, create this 17 collaborative opportunity for fundamental advancement. Our expert, integrated team of productive collaborators 18 aims to understand how the intrinsic features of tumor cells (Project 1), resident microglia (Project 2), and the 19 systemic immune system (Project 3) contribute to the onset and progression of brain metastases. These projects 20 are facilitated by centralized access to human patient brain metastases samples (NeuroPathology Core), and 21 novel, multiplexed analyses and disease modeling (ToolKit Core). Our multidisciplinary physician Consultant 22 Network provides clinical insight and helps in the rapid translation of our findings into clinical trials for patients 23 with brain metastases. The Administrative and Data Management Core will provide the operational support 24 necessary to successfully achieve the goals of the program. Our Patient Advocates help to integrate and 25 communicate our work to the greater scientific and patient communities. 26 We have formed one of the few groups with the expertise, interest, and capacity to address the underlying 27 mechanisms of and therapeutic opportunities for brain metastases. Only through this combined synergy would 28 this project be possible. These innovative methods will ensure our findings are reflective of and translatable to 29 the human disease, enabling our multidisciplinary team to lay the foundation for diagnostic and therapeutic 30 advancements.

1 摘要 – 总体组成部分 2 3 高达 40% 的癌症患者会出现脑转移，这标志着一个明显的拐点生存率和生活质量 4 分脑肿瘤组织的不可接近性阻碍了我们的进步。 5.了解和治疗脑转移瘤，并定期将患者排除在临床试验之外。 6 斯坦福脑转移联盟将脑部和癌症专家联合起来，共同致力于改善我们的脑转移 7 对脑转移瘤的理解和治疗，脑转移瘤是目前不断增加但服务不足的癌症子集为了实现上述8个目标，我们：（1）设计了支持的组织结构。 9 位科学家参与我们的综合工作；(2) 开发了高度创新和互补的项目来理解 10 并破坏支持脑转移的癌症-神经-免疫轴；(3) 创建了神经病理学； 11 和 ToolKit Cores 使参与者能够轻松获取人体标本和尖端技术 12 位科学家希望能够识别并靶向脑转移的关键介质，从而为患者带来治疗益处。 13名患者。 14 对于驱动肿瘤细胞进入大脑并让它们在大脑中生长的独特机制知之甚少。 15 个独特的微环境，部分由正常脑细胞支持。简化了对人脑的访问。 16 个标本，结合肿瘤微环境建模和操作方面的创新，创造了这个 17 实现根本性进步的协作机会我们的专家、综合团队富有成效的合作者。 18 旨在了解肿瘤细胞（项目 1）、常驻小胶质细胞（项目 2）和 19 全身免疫系统（项目 3）有助于脑转移的发生和进展。 20 通过集中访问人类患者脑转移样本（神经病理学核心）来促进，并且 21 种新颖的多重分析和疾病建模（ToolKit Core）。 22 Network 提供临床洞察力，帮助我们将研究结果快速转化为患者的临床试验 23 患有脑转移的患者，行政和数据管理核心将提供运营支持。 24 成功实现该计划目标所必需的，我们的患者倡导者帮助整合和实施。 25 将我们的工作传达给更广泛的科学界和患者界。 26 我们成立了少数几个拥有专业知识、兴趣和能力来解决潜在问题的团体之一。 27 脑转移的机制和治疗机会只有通过这种综合协同作用才能实现。 28 这些创新方法将确保我们的发现能够反映并转化为该项目。 29 人类疾病，使我们的多学科团队能够为诊断和治疗奠定基础 30 项进步。