Administrative Core

项目说明/摘要--行政核心 我们脑瘤治疗创新中心的目标是开发有效的新疗法 胶质母细胞瘤的治疗策略。所追求的主要策略集中在小说的最佳整合上 DNA损伤反应(DDR)抑制剂与标准护理遗传毒性药物，以增强作用 久经考验的疗法。应用于这个问题的总体框架包含了基本的肿瘤生物学。 DNA损伤信号与尖端药代动力学(PK)和药效学(PD)相结合 药物空间分布与效应评价及药物扰动信号系统分析 网络，以开发优化的治疗策略。临床前研究将使用大型、 高度特色化的患者来源异种移植(PDX)模型小组，这些研究的结果将是 用于指导两个项目的试点临床试验的发展。治疗评估核心将支持 执行这些动物和人体研究，药理学核心将支持PK和PD 对在这些动物和人类研究中获得的标本进行分析。计划进行高度集成的分析 这两个项目和两个核心将由行政核心组织和协助。这个 管理核心还将促进中心团队与更广泛的胶质瘤治疗公司的联系 网络。行政核心的职能大致可概括为五个具体目标： 目标1：为中心提供全面领导 目标2：指导项目和核心项目的科学规划和评价 目标3：促进项目和核心团队的整合和沟通 目标4：中心的行政管理 目标5：促进与胶质瘤治疗网络和外部合作者的互动

PROJECT DESCRIPTION/ABSTRACT – ADMINISTRATIVE CORE The goal for our Center of Innovation for Brain Tumor Therapeutics is to develop effective novel therapeutic strategies for glioblastoma (GBM). The primary strategy pursued is focused on optimal integration of novel DNA damage response (DDR) inhibitors with standard-of-care genotoxic agents to potentiate the effects of proven therapies. The overarching framework applied to this problem incorporates fundamental tumor biology of DNA damage signaling integrated with cutting edge pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of spatial drug distribution and effect and systems analysis of drug perturbation of signaling networks to develop optimized therapeutic strategies. Pre-clinical studies will be performed using a large, highly characterized panel of patient-derived xenograft (PDX) models, and results from these studies will be used to guide development of pilot clinical trials in both Projects. The Therapy Evaluation Core will support the execution of these animal and human studies, and the Pharmacology Core will support the PK and PD analysis of specimens obtained in these animal and human studies. The highly integrated analyses planned across the two Projects and two Cores will be organized and facilitated by the Administrative Core. The Administrative Core also will facilitate the connection of the Center team with the broader Glioma Therapeutics Network. Functions for the Administrative Core can be broadly characterized as five specific aims: Aim 1: Provide overall leadership for the Center Aim 2: Guide scientific planning and evaluation of Projects and Cores Aim 3: Foster integration and communication of Project and Core teams Aim 4: Administrative management of the Center Aim 5: Facilitate interactions with the Glioma Therapeutics Network and external collaborators