UCLA SPORE in Brain Cancer

加州大学洛杉矶分校孢子在脑癌中的应用

基本信息

批准号：
10673743
负责人：
Linda M Liau
金额：
$ 204.64万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-11 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10673743
关键词：
Active Immunotherapy Acute Address Apoptosis Apoptotic Area Awareness Basic Science Biochemistry Bioinformatics Biological Markers Biomedical Engineering Biometry Brain Brain Neoplasms CSF1R gene Cancer Patient Cell Death Cell Nucleus Cells Clinical Clinical Research Combined Modality Therapy Companions Development Diagnosis Discipline Disease Endocrinology Equilibrium Fostering Funding Future Glioblastoma Glioma Goals Grant Head and Neck Surgery Human Human Genetics Image Immune Evasion Immunology Immunotherapeutic agent Immunotherapy Industry Infrastructure Institution International Investigation Laboratories Leadership Magnetic Resonance Imaging Malignant neoplasm of brain Medicine Metabolism Microbiology Molecular Genetics Neurosciences Paper Pathology Patients Pediatrics Pharmaceutical Preparations Pharmacology Pharmacotherapy Phenotype Physicians Positron-Emission Tomography Prognosis Psychiatry Public Health Publishing Radiation Radiation Oncology Radiation therapy Radiology Specialty Reproduction spores Research Research Personnel Research Project Grants Research Support Resistance Resource Sharing Scientist Specimen Survival Rate Talents Technology Testing Translational Research United States National Institutes of Health Vaccination Work anticancer research cancer type career career development clinical care data management design human capital improved innovation multidisciplinary neoplastic cell neuroimaging new technology novel novel strategies novel therapeutic intervention novel therapeutics pre-clinical programmed cell death protein 1 programs stem cells therapy development therapy resistant translational approach translational research program tumor diagnosis tumor microenvironment

项目摘要

PROJECT SUMMARY/ABSTRACT – Overall The objectives of the UCLA SPORE in Brain Cancer are to contribute significantly to progress in the diagnosis, prognosis, and treatment of brain cancer. These goals will be accomplished through multiple and diverse research projects involving mechanistic pre-clinical work and innovative clinical studies, with a particular focus on developing novel strategies to overcome the problem of treatment-induced resistance. The broad, long-term objectives and aims of our brain cancer SPORE are as follows: 1) to investigate mechanisms of immunotherapy-induced immune evasion following active immunotherapy, and develop rational combinations of immunotherapeutic strategies to overcome the immunosuppressive milieu of the brain tumor microenvironment; 2) to elucidate the alterations in cellular metabolism associated with drug- induced resistance to apoptosis, and exploit targeting apoptotic blocks to induce intrinsic tumor cell death; and 3) to explore the concept of radiation-induced phenotype conversion of non-tumorigenic cells to glioblastoma-initiating cells as a mechanism for radiation-induced resistance, and test new therapeutics to block such glioma stem cell conversion. In order to achieve these translational research goals of our program, we propose three main projects involving: 1) targeting immunotherapy-induced resistance with DC vaccination and PD-1/CSF-1R inhibition; 2) overcoming drug-induced resistance to intrinsic apoptosis in glioblastoma; and 3) strategies against radiation-induced cellular plasticity in glioblastoma. These translational research projects will be supported by four shared resource cores in administration, biospecimen/pathology, neuroimaging, and biostatistics/bioinformatics. Our program has also been successful in actively incorporating researchers in our Developmental Research and Career Enhancement Programs in order to foster new approaches for assessing and treating brain cancer. Our diverse array of novel SPORE projects and state-of-the-art cores has already made a significant impact on brain cancer research during the last funding cycle, and we hope to continue to make impactful contributions to the field well into the future. Each project has been developed jointly by teams of basic and clinical researchers, with the thoughtful advisement of our internal advisory board (IAB) and external advisory board (EAB), working together in a trans-disciplinary manner to address the most vexing problem in brain cancer – the development of treatment resistance. All three proposed projects are highly translational and will reach new human endpoints within the context of our next SPORE grant period.

项目概要/摘要——总体加州大学洛杉矶分校 SPORE 在脑癌领域的目标是为脑癌领域的进展做出重大贡献脑癌的诊断、预后和治疗将通过多种方式实现。涉及机械临床前工作和创新临床研究的多样化研究项目，特别注重开发新策略来克服治疗引起的耐药性问题。我们脑癌 SPORE 的广泛、长期目标如下： 1) 调查主动免疫治疗后免疫治疗诱导的免疫逃避机制，并开发合理组合免疫治疗策略以克服免疫抑制环境脑肿瘤微环境；2）阐明与药物相关的细胞代谢变化诱导细胞凋亡抵抗，并利用靶向细胞凋亡阻断来诱导内在的肿瘤细胞死亡； 3) 探索辐射诱导的非致瘤细胞表型转变的概念胶质母细胞瘤起始细胞作为辐射诱导抵抗的机制，并测试新的疗法阻止这种神经胶质瘤干细胞转化为了实现我们计划的这些转化研究目标，我们提出了三个主要项目，涉及：1）用 DC 靶向免疫疗法诱导的耐药性疫苗接种和 PD-1/CSF-1R 抑制；2) 克服药物诱导的内在细胞凋亡抗性；胶质母细胞瘤；3) 对抗放射诱导的胶质母细胞瘤细胞可塑性的策略。转化研究项目将得到行政管理领域四个共享资源核心的支持，我们的项目还包括生物样本/病理学、神经影像学和生物统计学/生物信息学。成功地将研究人员积极纳入我们的发展研究和职业提升旨在培育评估和治疗脑癌的新方法的计划。新颖的 SPORE 项目和最先进的核心已经对脑癌产生了重大影响在上一个资助周期进行研究，我们希望继续为该领域做出有影响力的贡献每个项目都是由基础研究人员和临床研究人员团队共同开发的。我们的内部顾问委员会 (IAB) 和外部顾问委员会 (EAB) 的深思熟虑的建议，以跨学科的方式共同解决脑癌中最棘手的问题——发展所有三个拟议项目都具有高度转化性，并将惠及新人类。我们下一个 SPORE 资助期内的端点。