SPORE in Brain Cancer

描述（由申请人提供）： 这个杜克脑肿瘤孢子补助金包括四个项目，五个核心，一个发展研究计划和一个职业发展计划。拟议研究的目标是推进脑肿瘤生物学和病因学的知识，并将其转化为临床方案，代表这些治疗难治性肿瘤管理的重大和新进展。赠款，作为一个整体，每个项目和核心，是由基础和临床首席研究员领导。在项目1中，针对恶性胶质瘤中过表达和预后不良指标的GST 1蛋白的新型疗法将被合理开发并评估临床疗效。项目2将研究CNS肿瘤对Temodar（一种临床活性脑肿瘤药物）耐药的新分子机制，并评估PARP抑制剂逆转Temodar耐药的临床疗效。项目3将研究基于树突状细胞的CMV疫苗接种作为恶性胶质瘤的治疗方式和抗肿瘤反应的潜在机制。在项目4中，分子和流行病学研究将在病例对照研究中检查脑肿瘤的病因。暴露于假定的神经致癌物将进行检查，代谢和DNA修复基因的多态性将作为脑肿瘤风险和治疗相关毒性的决定因素进行检查。这些核心包括组织采购和遗传学核心、研究性新药许可核心、I/II期临床试验核心、生物统计和信息系统核心以及将提供关键基础设施和服务功能的行政核心。 发展研究计划将包括从杜克癌症中心全体成员以及选定的外部机构中确定的试点项目。重点是以前没有在神经肿瘤学工作过的研究人员。九个试点项目的例子，从高级研究人员在杜克谁没有以前的工作对脑肿瘤包括在内。

DESCRIPTION (provided by applicant): This Duke Brain Tumor SPORE grant consists of four projects, five cores, a Developmental Research Program, and a Career Development Program. The goal of the proposed research is to advance knowledge of brain tumor biology and etiology and to translate these into clinical protocols that represent significant and novel advances in the management of these therapeutically intractable tumors. The grant, as a whole, and each project and core, are led by basic and clinical Principal Investigators. In Project 1, novel therapeutics that target the GSTP1 protein, overexpressed and a poor prognostic indicator in malignant gliomas, will be rationally developed and evaluated for clinical efficacy. Project 2 will investigate novel molecular mechanisms of resistance of CNS tumors to Temodar, a clinically active brain tumor agent and evaluate the clinical efficacy of a PARP inhibitor in reversing Temodar resistance. Project 3 will investigate dendritic cell-based vaccination against CMV as a therapeutic modality in malignant glioma and the underlying mechanisms of the anti-tumor response. In Project 4, molecular and epidemiologic studies will examine the etiology of brain tumors in a case-control study. Exposure to putative neurocarcinogens will be examined and polymorphisms in metabolism and DNA repair genes will be examined as a determinant of brain tumor risk and treatment-associated toxicity. The cores include a Tissue Procurement and Genetics Core, an Investigational New Drug Permit Core, a Phase I/II Clinical Trials Core, a Biostatistics and Information Systems Core, and an Administrative Core which will provide critical infrastructural and service functions. The Developmental Research Program will consist of pilot projects identified from the entire Cancer Center membership at Duke as well as from selected, outside institutions. Emphasis is on investigators who have not previously worked in neuro-oncology. Nine examples of pilot projects from senior investigators at Duke who have not previously worked on brain tumors are included.