BRAIN TUMOR SPORE GRANT

描述（由申请人提供）：此SPORE更新申请代表了UCSF综合癌症中心神经肿瘤学项目研究人员的跨学科团队的努力，将他们的知识和专业知识应用于专注于脑肿瘤的转化研究。该应用程序的核心是五个转化研究项目，每个项目都由应用和基础研究人员团队驱动，每个项目都旨在创建可用于治疗脑肿瘤的新工具和疗法。项目一是一个非常成功的人口科学项目的延伸，旨在确定胶质瘤患者生存的重要因素。项目二是一个非常成功的成像项目的延伸，该项目旨在使用复杂的光谱技术来非侵入性地定义预测低级别胶质瘤生物学的因素。项目三建立在前一个资助期开发的新型含药纳米颗粒的基础上，并提出生产和测试新的治疗性纳米颗粒，其分布可以通过对流增强输送控制，并通过光谱学进行真实的实时监测。项目四提出了基于实验室和临床的研究，旨在澄清和利用之前资助期间发现的Akt激活与EGFR抑制剂厄洛替尼敏感性之间的负相关性。项目五是由上一个资助期的两个发展研究项目的融合发展而来的，它提出了基于实验室和临床的研究，旨在研究和利用PTEN/Akt/mTOR通路在神经胶质瘤疫苗治疗中的作用。申请还要求继续支持非常成功的职业发展和发展研究计划，以及四个核心（现有的组织和行政核心以及新的动物和生物统计学/临床核心），这将支持工作的各个方面。每个项目都借鉴了研究人员在脑肿瘤研究方面的丰富经验，以及UCSF神经外科系和UCSF脑肿瘤研究中心的转化脑肿瘤研究的悠久历史。这些项目将通过与UCSF综合癌症中心和UCSF乳腺和前列腺孢子科学家的合作得到进一步加强。最后，作为美国领先的脑肿瘤临床试验中心，UCSF神经肿瘤学项目的基础设施已经到位，可以快速临床转化重要的科学发现。 UCSF脑肿瘤孢子的主要研究者是Mitchel Berger，医学博士，神经外科和转化脑肿瘤研究的国家公认的领导者。本申请的临床共同主要研究者是Michael Prados，MD，他是北美脑肿瘤联盟的主要研究者，也是脑肿瘤临床试验开发和实施的公认领导者。本申请的基础科学合作PI是Russell Pieper博士，他是UCSF神经肿瘤学项目和UCSF脑肿瘤研究中心的基础科学主任，也是胶质瘤细胞信号研究的公认领导者。领导团队的行政，临床和实验室经验，沿着强大的跨学科研究团队和UCSF强大的研究氛围表明，拟议的工作将导致脑肿瘤治疗的重大进展。

DESCRIPTION (provided by applicant): This SPORE renewal application represents the efforts of interdisciplinary teams of investigators from the Neuro-Oncology Program of the UCSF Comprehensive Cancer Center to apply their knowledge and expertise to translational research focused on brain tumors. The heart of the application is five translational research projects, each driven by teams of applied and basic investigators, and each intended to create novel tools and therapies useful in the treatment of brain tumors. Project One is an extension of a highly successful population science project that intends to define factors important in glioma patient survival. Project Two is an extension of a highly successful imaging project that intends to use sophisticated spectroscopic techniques to non-invasively define factors that predict low-grade glioma biology. Project Three builds on novel drug-containing lipidic nanoparticles developed in the previous funding period, and proposes to generate and test new therapeutic nanoparticles whose distribution can be controlled by convection-enhanced delivery and monitored in real time spectroscopically. Project Four proposes lab based and clinical studies intended to clarify and exploit the negative association discovered in the previous funding period between Akt activation and sensitivity to the EGFR inhibitor erlotinib. Project Five, which evolved from the convergence of two Developmental Research Projects in the previous funding period, proposes lab-based and clinical studies intended to investigate and exploit the role the PTEN/Akt/mTOR pathway plays in response to glioma vaccine therapy. The application also requests continued support for highly successful Career Development and Developmental Research Programs, and for four Cores (the existing Tissue and Administrative Cores and the new Animal and Biostatistics/Clinical Core) that will support all aspects of the work. Each project draws on the extensive experience of the investigators in brain tumor research, and on the long history of translational brain tumor research in the UCSF Department of Neurological Surgery and UCSF Brain Tumor Research Center. The projects will be additionally strengthened by collaborations with scientists in the UCSF Comprehensive Cancer Center and in the UCSF Breast and Prostate SPOREs. Finally, as a leading center of brain tumor clinical trials in America, an infrastructure is in place in the UCSF Neuro-Oncology Program to allow rapid clinical translation of important scientific discoveries. The Principal Investigator of the UCSF Brain Tumor SPORE is Mitchel Berger, MD, a nationally recognized leader in neurosurgery and translational brain tumor research. The clinical co-PI of this application is Michael Prados, MD, the PI of the North American Brain Tumor Consortium and a recognized leader in the development and implementation of clinical trials in brain tumors. The basic science co-PI of this application is Russell Pieper, PhD, the Basic Science Director of the UCSF Neuro-Oncology Program and the UCSF Brain Tumor Research Center and a recognized leader in the study of cell signaling in gliomas. The combined administrative, clinical, and lab-based experience of the leadership team, along with the strong interdisciplinary research teams and the strong research climate at UCSF suggest that the work proposed will lead to significant progress in the treatment of brain tumors.