Biomarker, Bioinformatics and Biorepository Core

项目摘要-生物标记物、生物信息学和生物信息库核心 杜克大学西南胶质母细胞瘤治疗网络(GTN)团队将完成临床前研究 胶质母细胞瘤(GBM)新疗法(6-硫代-DG)的研制及生物学研究 早期临床试验中的活动。这个生物标记、生物信息学和生物信息库核心(Bio-Mir Core)将 通过1)提供后勤、生物标记物、生物统计学、生物信息学和生物库支持来支持这项任务 这使得GTN团队的研究人员能够优化对GBM患者的6-硫代-DG治疗，以及2)服务 作为其他GTN站点的资源，使更广泛的网络能够访问相同的专业知识和组织。 Bio-Mir核心对于成功进行本申请中提出的研究是不可或缺的， 包括6-硫代-DG的早期临床试验，通过标准化组织收集和 集中分析患者资格和肿瘤对6-硫代-DG治疗反应的关键生物标记物(目标1)。 我们将通过对以前切除的肿瘤和 使用CLIA批准的试验确定IDH1/2和TERT启动子突变状态以确定是否符合 注射6-硫代-DG。在6-硫代-DG治疗和肿瘤切除之后，Bio-Mir Core将再次监督 中枢神经病理学回顾和药效学终点测量，包括γH_2AX测量 损害(主要试验终点)。Bio-Mir核心将提供生物库服务，用于收集、处理 并在CAP认证的环境中存储所有GBM患者组织，并将这些组织分布在 杜克大学/UTSW GTN和所有GTN站点(目标2)。Bio-Mir核心还将提供生物统计和 生物信息学专业知识，用于进行、分析和报告相关研究，并确保数据完整性 通过集中整合临床数据，包括多平台数据整合和协调(目标3)。 此外，Bio-Mir核心将促进一种模范的研究文化，其中最佳数据管理做法 贯穿始终，以确保研究结果的数据完整性、来源、安全性和重复性。生物-- MIR Core将受益于机构和NIH对关键共享资源的投资，包括临床 数据仓库和多机构生物库和标本共享，并利用 进行了30多年多中心GBM研究的调查人员。Bio-Mir核心 将促进GTN调查人员之间的合作，并将与指定的网络合作 跨GTN资源共享和参与先进疗法临床试验协调中心 由GTN指导委员会进行多中心评价。通过这种方式，Bio-Mir核心将充当 帮助实现GTN开发新的、有效的代理人的总体目标的不可或缺的资源 跨越血脑屏障，在临床上进行检测，以提高成人GBM的治疗水平。

PROJECT SUMMARY – Biomarker, Bioinformatics and Biorepository Core The Duke/UT Southwestern Glioblastoma Therapeutics Network (GTN) team will complete pre-clinical development of a novel treatment (6-thio-dG) for patients with glioblastoma (GBM) and investigate its biologic activity in an early-phase clinical trial. This Biomarker, Bioinformatics and Biorepository Core (Bio-MIR Core) will support this mission by 1) providing logistical, biomarker, biostatistical, bioinformatic and biorepository support that enables this GTN team’s investigators to optimize 6-thio-dG treatment for patients with GBM, and 2) serving as a resource to other GTN sites by enabling the broader network to access the same expertise and tissues. The Bio-MIR Core will be indispensable for the successful conduct of the studies proposed in this application, including the early-phase clinical trial of 6-thio-dG, by standardizing protocols for the collection of tissues and centralizing analyses of key biomarkers of patient eligibility and tumor response to 6-thio-dG treatment (Aim 1). We will provide expert neuropathologic consultation through central review of previously resected tumors and ascertain IDH1/2 and TERT-promoter mutation status using CLIA-approved assays to determine eligibility to receive 6-thio-dG. Following 6-thio-dG treatment and tumor resection, the Bio-MIR Core will again oversee central neuropathologic review and measure pharmacodynamic endpoints, including γH2AX measures of DNA damage (primary trial endpoint). The Bio-MIR Core will provide biobanking services for the collection, processing and storage of all GBM patient tissues in a CAP-certified setting, and distribute these tissues both within the Duke/UTSW GTN and across all GTN sites (Aim 2). The Bio-MIR Core will also provide biostatistics and bioinformatics expertise for the conduct, analysis, and reporting of correlative studies, and ensure data integrity through centralized integration of clinical data, including multi-platform data integration and coordination (Aim 3). Further, the Bio-MIR Core will promote an exemplary research culture wherein best data management practices are used throughout to ensure data integrity, provenance, security, and reproducibility of study findings. The Bio- MIR Core will benefit from institutional and NIH investments made in key shared resources, including clinical data warehousing and multi-institutional biobanking and specimen sharing, and utilize the expertise of investigators that have conducted multi-center GBM research for more than three decades. The Bio-MIR Core will facilitate collaboration between GTN investigators and will also work with the designated Network Coordination Center for trans-GTN sharing of resources and participation in clinical trials of therapies advanced by the GTN Steering Committee to multi-center evaluations. In this manner, the Bio-MIR Core will serve as an indispensable resource helping to achieve the GTN’s overall goal of developing novel, effective agents that can cross the blood-brain-barrier and testing them in the clinic to improve treatment for adults with GBM.