UCLA SPORE in Brain Cancer

总体：UCLA SPORE在脑癌 总结/摘要 加州大学洛杉矶分校的目标是在脑癌的孢子是作出重大贡献的进展， 脑癌的诊断、预后和治疗。这些目标将通过多种途径实现， 涉及机械临床前工作和创新临床研究的各种研究项目， 特别注重开发新的战略，以克服耐药性问题。那个女人 我们的脑癌SPORE的长期目标和目的如下：1）研究 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 与靶向治疗耐药性相关的代谢改变，并利用这些代谢 探讨辐射诱导肿瘤细胞凋亡的概念， 非致瘤细胞表型转化为胶质母细胞瘤起始细胞作为辐射机制 耐药性，并测试新的治疗方法来阻断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敏化IDH突变体 神经胶质瘤的治疗为了实现我们计划的这些转化研究目标，我们提出四个 主要项目涉及：1）主动免疫疗法结合免疫检查点调节， 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 表型转化为神经胶质瘤起始干细胞;和4）IDH突变体的新表观遗传治疗 神经胶质瘤这些转化研究项目将得到行政管理方面的共享资源核心的支持， 生物标本/病理学、神经成像和生物统计学/生物信息学/数据管理。我们的计划将 还通过整合发展研究和职业提升来响应SPORE主题 计划，以促进评估和治疗脑癌的新方法。我们多样化的 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团队共同开发的， 以跨学科的方式解决脑癌中最令人烦恼的问题-治疗的发展 阻力所有四个项目都是高度转化的，并将在此背景下达到人类终点。 孢子授予期间。

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.