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: 10225544
• 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/10225544
• 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; Prognosis; 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; pre-clinical; programs; radiation resistance; resistance mechanism; stem cells; 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.

总而言之：加州大学洛杉矶分校的孢子在脑癌中 摘要/摘要 加州大学洛杉矶分校分生孢子在脑癌方面的目标是为脑癌研究的进展做出重大贡献 脑癌的诊断、预后和治疗。这些目标将通过多个和 涉及机械性临床前工作和创新临床研究的各种研究项目，具有 特别注重开发新的战略，以克服治疗耐药性问题。宽阔的， 我们的脑癌孢子的长期目标和目标如下：1)研究脑癌孢子的作用机制 主动免疫治疗后的免疫逃避，并开发免疫治疗的合理组合 克服脑肿瘤微环境免疫抑制环境的策略；2)阐明 与靶向治疗抵抗相关的代谢变化，并利用这些代谢 脆弱性诱导肿瘤细胞内源性凋亡；3)探讨辐射诱导的概念 非致瘤细胞向胶质母细胞瘤起始细胞的表型转化作为辐射的机制 抗药性，并测试新的治疗方法来阻止这种胶质瘤干细胞转化；以及4)研究 IDH抑制剂的抗性途径，并利用新的表观遗传途径使IDH突变体增敏 神经胶质瘤需要治疗。为了实现我们项目的这些翻译研究目标，我们提出了四个 主要项目包括：1)主动免疫治疗结合免疫检查点调节治疗 胶质母细胞瘤；2)针对胶质母细胞瘤细胞的代谢易损性；3)抑制辐射诱导 向胶质瘤起始干细胞的表型转化；以及4)IDH突变体的新表观遗传学治疗 神经胶质瘤。这些转化性研究项目将得到管理上的共享资源核心的支持， 生物医学/病理学、神经成像和生物统计学/生物信息学/数据管理。我们的节目将 也通过结合发展研究和职业提升来响应孢子主题 计划，以促进评估和治疗脑癌的新方法。我们种类繁多的 新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和临床研究人员组成的团队共同开发的 以跨学科的方式解决脑癌最棘手的问题-治疗的发展 抵抗。所有四个项目都具有很高的翻译性，并将在此上下文中到达人类端点 孢子授权期。