BRAIN TUMOR SPORE GRANT

描述(由申请人提供)：这份孢子更新申请代表了加州大学旧金山分校综合癌症中心神经肿瘤学项目的跨学科研究团队努力将他们的知识和专业知识应用于专注于脑瘤的翻译研究。该应用程序的核心是五个转化性研究项目，每个项目都由应用和基础研究团队推动，每个项目都旨在创造对脑瘤治疗有用的新工具和疗法。第一个项目是一个非常成功的人口科学项目的延伸，该项目旨在确定对胶质瘤患者生存至关重要的因素。项目二是一个非常成功的成像项目的扩展，该项目打算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物脂类纳米颗粒的基础上，并提议产生和测试新的治疗纳米颗粒，其分布可以通过对流增强输送来控制，并通过光谱实时监测。项目四提出了基于实验室和临床的研究，旨在澄清和利用在之前的资助期发现的Akt激活与对EGFR抑制剂erlotinib的敏感性之间的负关联。项目5是由前一资助时期的两个发展研究项目合并而来的，它提出了基于实验室和临床的研究，旨在调查和开发PTEN/Akt/mTOR通路在胶质瘤疫苗治疗中所起的作用。申请还要求继续支持非常成功的职业发展和发展研究方案，以及将支持工作所有方面的四个核心(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)。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，以及加州大学旧金山分校神经外科和加州大学脑肿瘤研究中心在翻译性脑瘤研究方面的悠久历史。这些项目将通过与加州大学旧金山分校综合癌症中心以及加州大学旧金山分校乳房和前列腺癌孢子的科学家合作而得到进一步加强。最后，作为美国领先的脑瘤临床试验中心，加州大学旧金山分校的神经肿瘤学项目已经建立了一个基础设施，使重要的科学发现能够快速转化为临床。 加州大学旧金山分校脑瘤孢子的首席研究员是医学博士Mitchel Berger，他是全国公认的神经外科和转化性脑瘤研究的领导者。该应用程序的临床合作者是Michael Prados医学博士，他是北美脑瘤协会的PI，也是开发和实施脑瘤临床试验的公认领导者。这一应用程序的基础科学合作PI是Russell Pieper博士，他是加州大学旧金山分校神经肿瘤学项目和加州大学旧金山分校脑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。领导团队的管理、临床和实验室经验的结合，加上强大的跨学科研究团队和加州大学旧金山分校浓厚的研究氛围，表明拟议的工作将在脑瘤治疗方面取得重大进展。

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.