Administrative Core

行政核心

• 批准号: 10305362
• 负责人: Jann N. Sarkaria
• 金额: $ 12.11万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10305362
• 关键词: Animals; Brain Neoplasms; Clinical Trials; Collaborations; Communication; Contracts; DNA Damage; Development; Ensure; Evaluation; Fostering; Glioblastoma; Glioma; Goals; Human; Institution; Lead; Leadership; Link; Logistics; Manuscripts; Mutagens; Office of Administrative Management; Pharmaceutical Preparations; Pharmacology; Pilot Projects; Quality Control; Recommendation; Reproducibility; Research Personnel; Resources; Services; Signal Transduction; Specimen; Systems Analysis; Therapeutic; Therapy Evaluation; Tumor Biology; data sharing; drug distribution; industry partner; inhibitor/antagonist; innovation; meetings; novel; novel therapeutic intervention; patient derived xenograft model; pharmacokinetics and pharmacodynamics; preclinical study; response; standard of care

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

项目描述/摘要-行政核心 我们的脑肿瘤治疗创新中心的目标是开发有效的新型治疗方法， 胶质母细胞瘤（GBM）的治疗策略。追求的主要战略是集中在最佳整合的新的 DNA损伤反应（DDR）抑制剂与标准治疗遗传毒性剂联合使用，以增强 经过验证的疗法。应用于这个问题的总体框架包括基本的肿瘤生物学 DNA损伤信号传导与尖端药代动力学（PK）和药效学（PD）相结合 药物空间分布和效应评价及药物干扰信号的系统分析 网络来开发优化的治疗策略。临床前研究将使用大型， 高度表征的一组患者来源的异种移植物（PDX）模型，这些研究的结果将被 用于指导两个项目中的试点临床试验的开发。治疗评价核心将支持 执行这些动物和人体研究，药理学核心将支持PK和PD 分析这些动物和人体研究中获得的标本。计划进行的高度综合分析 两个项目和两个核心的协调工作将由行政核心组织和推动。的 行政核心还将促进中心团队与更广泛的胶质瘤治疗学的联系 网络行政核心的职能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：指导项目和核心的科学规划和评估 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