UCLA SPORE in Brain Cancer

项目总结/摘要-总体 加州大学洛杉矶分校脑癌SPORE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。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， 特别关注开发新的策略来克服治疗诱导的抗性问题。 我们的脑癌SPORE的广泛，长期目标和目的如下：1）调查 主动免疫治疗后免疫治疗诱导的免疫逃避机制，并发展 免疫抑制策略的合理组合，以克服免疫抑制的环境， 脑肿瘤微环境; 2）阐明与药物相关的细胞代谢的改变， 诱导对凋亡的抗性，并利用靶向凋亡阻断剂诱导内源性肿瘤细胞死亡; 探讨辐射诱导非致瘤细胞表型转化的概念， 胶质母细胞瘤起始细胞作为辐射诱导抗性的机制，并测试新的治疗方法， 阻断这种胶质瘤干细胞转化。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，包括：1）用DC靶向免疫治疗诱导的耐药性 疫苗接种和PD-1/CSF-1 R抑制; 2）克服药物诱导的对内源性细胞凋亡的抗性， 胶质母细胞瘤;和3）对抗胶质母细胞瘤中辐射诱导的细胞可塑性的策略。这些 翻译研究项目将得到四个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。我们的计划也是 成功地将研究人员积极纳入我们的发展研究和职业发展 计划，以促进评估和治疗脑癌的新方法。我们多样化的 新的孢子项目和最先进的核心已经对脑癌产生了重大影响 我们在上一个资助周期进行了研究，我们希望继续为该领域做出有影响力的贡献。 在未来很久。每个项目都是由基础和临床研究人员团队共同开发的， 我们的内部咨询委员会（IAB）和外部咨询委员会（EAB）的周到安排， 以跨学科的方式共同解决脑癌中最令人烦恼的问题-发展 治疗抵抗。所有这三个项目都是高度翻译的，将达到新的人类 在我们的下一个SPORE授予期内的端点。

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.