SPORE in Brain Cancer

描述(由申请人提供)： 这项杜克大学脑瘤孢子基金由四个项目、五个核心、一个发展研究计划和一个职业发展计划组成。这项拟议研究的目标是促进脑肿瘤生物学和病因学的知识，并将这些知识转化为临床方案，代表着在这些治疗难治肿瘤的管理方面取得的重大和新的进展。补助金作为一个整体，以及每个项目和核心，都由基础和临床首席研究员领导。在项目1中，将合理开发针对GSTP1蛋白的新疗法，并对其临床疗效进行评估。GSTP1蛋白过度表达，是恶性胶质瘤预后较差的指标。项目2将研究中枢神经系统肿瘤对临床活性脑肿瘤药物泰莫达耐药的新分子机制，并评估PARP抑制剂在逆转泰莫达耐药性方面的临床疗效。项目3将研究以树突状细胞为基础的巨细胞病毒疫苗作为恶性胶质瘤的一种治疗方式以及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学。研究人员将检查可能的神经致癌物质的暴露情况，并将新陈代谢和DNA修复基因的多态性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、研究新药许可核心、第一阶段/第二阶段临床试验核心、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大学整个癌症中心成员以及选定的外部机构确定的试点项目。重点是那些以前没有从事过神经肿瘤学工作的研究人员。其中包括9个来自杜克大学高级调查人员的试点项目，他们以前没有研究过脑瘤。

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.