UCLA SPORE in Brain Cancer

加州大学洛杉矶分校孢子在脑癌中的应用

• 批准号: 9752960
• 负责人: Linda M Liau
• 金额: $ 213.9万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 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/9752960
• 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; Immunosuppressive Agents; 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; Stem cells; 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; targeted treatment; therapy development; therapy resistant; translational approach; translational research program; tumor microenvironment

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：脑癌的UCLA孢子 摘要/摘要 加州大学洛杉矶分校孢子在脑癌中的目标将为进步做出重大贡献 诊断，预后和治疗脑癌。这些目标将通过多个和 潜水员研究项目涉及机械临床前工作和创新临床研究， 特别着眼于制定新的策略来克服耐药性问题。广泛， 我们的脑癌孢子的长期目标和目标如下：1）研究机制 主动免疫疗法后的免疫进化，并发展出免疫治疗的合理组合 克服脑肿瘤微环境的免疫抑制环境的策略； 2）阐明 与靶向治疗抗性相关的代谢的改变，并利用这些代谢 诱导肿瘤细胞内在凋亡的脆弱性； 3）探索辐射引起的概念 非肿瘤细胞向胶质母细胞瘤发射细胞的表型转化为辐射机制 抗性和测试新疗法以阻断这种神经胶质瘤干细胞转化； 4）调查 对IDH抑制剂的抗性途径，并利用敏感IDH突变剂的新型表观遗传途径 胶质瘤进行治疗。为了实现我们计划的这些翻译研究目标，我们提出了四个 涉及的主要项目：1）主动免疫疗法与免疫定位调制相结合 胶质母细胞瘤； 2）靶向胶质母细胞瘤细胞中的代谢脆弱性； 3）抑制辐射诱导的 表型转化为胶质瘤发射干细胞； 4）IDH突变体的新型表观遗传治疗 神经胶质瘤。这些翻译研究项目将得到管理中共享的资源核心的支持， 生物测定/病理学，神经影像学和生物统计学/生物信息学/数据管理。我们的计划将 还通过结合发展研究和职业增强来响应孢子主题 为了培养评估和治疗脑癌的新方法。我们的潜水员阵列 新颖的项目和最先进的核心可能会对脑癌患者护理产生重大影响。 每个项目都是由基本和临床研究人员共同开发的 跨学科的方式解决脑癌中最烦人的问题 - 治疗的发展 反抗。这四个项目都经过高度翻译，并将在此背景下达到人类终点 孢子赠款期。