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：
9982853
负责人：
Linda M Liau
金额：
$ 218.5万
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 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9982853
关键词：
Active Immunotherapy Acute Address Apoptosis Area Awareness Basic Science Bioinformatics Biological Markers Biometry Brain Brain Neoplasms California Cancer Patient Cells Clinic Clinical Clinical Research Clinical Trials Communities Companions Comprehensive Cancer Center Country Detection Development Diagnosis Disease Epigenetic Process Equilibrium Fostering Funding Glioblastoma Glioma Goals Grant Human Image Immune Evasion Immunotherapeutic agent Infrastructure International Knowledge Magnetic Resonance Imaging Malignant neoplasm of brain Metabolic Metabolism NCI Center for Cancer Research Paper Pathology Pathway interactions Patient Care Patients Phenotype Positron-Emission Tomography Public Health Publishing Radiation Reproduction spores Research Research Personnel Research Project Grants Research Support Resistance Resource Sharing Resources Scientist Specimen Survival Rate Testing Translational Research Translations United States National Institutes of Health Work anticancer research cancer type career career development checkpoint modulation clinical care clinical practice data management design immune checkpoint improved inhibitor/antagonist innovation mutant neoplastic cell neuro-oncology neuroimaging neurosurgery novel novel strategies novel therapeutic intervention novel therapeutics oncology program outcome forecast pre-clinical programs radiation resistance resistance mechanism stem cells targeted treatment therapy development therapy resistant translational approach translational research program tumor microenvironment

项目摘要

Overall: UCLA SPORE in Brain Cancer SUMMARY/ABSTRACT 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 resistance. The broad, long-term objectives and aims of our brain cancer SPORE are as follows: 1) to investigate mechanisms of 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 metabolism associated with targeted therapy resistance, and exploit these metabolic vulnerabilities to induce intrinsic apoptosis of tumor cells; 3) to explore the concept of radiation-induced phenotype conversion of non-tumorigenic cells to glioblastoma-initiating cells as a mechanism for radiation resistance, and test new therapeutics to block such glioma stem cell conversion; and 4) to investigate the pathways of resistance to IDH inhibitors, and utilize novel epigenetic pathways to sensitize IDH-mutant gliomas to treatment. In order to achieve these translational research goals of our program, we propose four main projects involving: 1) active immunotherapy combined with immune checkpoint modulation for glioblastoma; 2) targeting metabolic vulnerabilities in glioblastoma cells; 3) inhibition of radiation-induced phenotype conversion to glioma-initiating stem cells; and 4) novel epigenetic treatment of IDH mutant gliomas. These translational research projects will be supported by shared resource cores in administration, biospecimen/pathology, neuroimaging, and biostatistics/bioinformatics/data management. Our program will also be responsive to SPORE themes by incorporating Developmental Research and Career Enhancement Programs in order to foster new approaches for assessing and treating brain cancer. Our diverse array of novel projects and state-of-the-art cores will likely make a significant impact on brain cancer patient care. Each project has been developed jointly by teams of basic and clinical researchers working together in a trans-disciplinary manner to address the most vexing problem in brain cancer – the development of treatment resistance. All four projects are highly translational and will reach human endpoints within the context of this SPORE grant period.

总体而言：UCLA SPORE 在脑癌中的应用摘要/摘要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，特别关注开发新策略来克服广泛的治疗耐药性问题。我们脑癌SPORE的长期目标如下：1）研究脑癌SPORE的机制主动免疫治疗后的免疫逃避，并开发合理的免疫治疗组合克服脑肿瘤微环境的免疫抑制环境的策略2) 阐明；与靶向治疗耐药相关的代谢变化，并利用这些代谢诱导肿瘤细胞内在凋亡的脆弱性；3）探索辐射诱导的概念；非致瘤细胞向胶质母细胞瘤起始细胞的表型转化作为放射机制耐药性，并测试新的疗法来阻止这种神经胶质瘤干细胞转化；4) 研究 IDH 抑制剂耐药途径，并利用新的表观遗传途径使 IDH 突变体敏感为了实现我们计划的这些转化研究目标，我们提出了四个建议。主要项目涉及：1）主动免疫疗法联合免疫检查点调节胶质母细胞瘤；2) 针对胶质母细胞瘤细胞的代谢脆弱性；3) 抑制辐射诱导的 4) IDH突变体的新型表观遗传学治疗这些转化研究项目将得到行政管理共享资源核心的支持，我们的计划将包括生物样本/病理学、神经影像学和生物统计学/生物信息学/数据管理。还通过结合发展研究和职业提升来响应 SPORE 主题旨在培育评估和治疗脑癌的新方法的计划。新颖的项目和最先进的核心可能会对脑癌患者的护理产生重大影响。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跨学科方式解决脑癌最棘手的问题——治疗方法的发展所有四个项目都具有高度转化性，并将在此背景下达到人类终点。孢子授予期。