Administrative Core

行政核心

• 批准号: 10704625
• 负责人: Jann N. Sarkaria
• 金额: $ 22.89万
• 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/10704625
• 关键词: Animals; Brain Neoplasms; Clinical Trials; Collaborations; Communication; 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; 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 我们脑肿瘤治疗创新中心的目标是开发有效的新型疗法 胶质母细胞瘤（GBM）的策略所追求的主要策略集中于新型药物的最佳整合。 DNA 损伤反应 (DDR) 抑制剂与标准护理基因毒性药物可增强 DNA 损伤反应 (DDR) 抑制剂的作用 应用于该问题的总体框架结合了基本的肿瘤生物学。 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估以及药物信号扰动的系统分析 将使用大型的、开发优化治疗策略的网络进行。 高度特征化的患者来源异种移植（PDX）模型组，这些研究的结果将 用于指导这两个项目的试点临床试验的开发。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 计划对这些动物和人类研究中获得的标本进行高度综合的分析。 跨两个项目和两个核心的工作将由行政核心组织和促进。 行政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。行政核心的职能可概括为五个具体目标： 目标1：为中心提供全面领导 目标二：指导项目和核心科学规划和评估 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：促进与神经胶质瘤治疗网络和外部合作者的互动