Biomarker, Bioinformatics and Biorepository Core

生物标志物、生物信息学和生物样本库核心

基本信息

批准号：
10488239
负责人：
ROGER E MCLENDON
金额：
$ 5.18万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-13 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10488239
关键词：
Adult American Association of Cancer Research Award Bioinformatics Biological Biological Assay Biological Markers Biological Specimen Banks Biometry Blood Blood - brain barrier anatomy Blood specimen Brain Neoplasms CLIA certified Cells Clinic Clinical Data Clinical Research Collaborations Collection Consultations Correlative Study DNA Damage DNA sequencing Data Databases Deoxyguanosine Drug or chemical Tissue Distribution Eligibility Determination Ensure Evaluation Excision Faculty Foundations Freezing Funding Gamma-H2AX Genomics Genotype Glioblastoma Goals Immune Immunologic Markers Infiltration Informatics Institution Interphase Investments Laboratories Logistics Measurement Measures Mediating Methods Mission Patients Pharmacodynamics Phase 0 Trial Phenotype Pilot Projects Practice Management Prognostic Marker Protocols documentation Reporting Reproducibility Research Research Personnel Research Support Resected Resource Sharing Resources Science Security Services Site Specimen Standardization Stimulator of Interferon Genes Telomerase Testing Therapeutic Therapy Clinical Trials Tissue Banks Tissue Procurements Tissues Training Tumor Tissue Tumor-infiltrating immune cells United States National Institutes of Health Work anti-tumor immune response base biobank biomarker discovery clinical data warehouse clinical decision-making data integration data integrity data management early phase clinical trial experience gene panel good laboratory practice human tissue immunogenic improved industry partner innate immune sensing molecular marker mutational status neuro-oncology next generation novel novel therapeutics patient biomarkers preclinical development predictive marker primary endpoint prognostic value promoter response telomere testing services transcriptome sequencing tumor

项目摘要

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.

项目摘要 – 生物标志物、生物信息学和生物样本库核心杜克大学/德克萨斯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开发一种治疗胶质母细胞瘤 (GBM) 患者的新疗法 (6-thio-dG) 并研究其生物学该生物标志物、生物信息学和生物库核心（Bio-MIR Core）将开展早期临床试验。通过 1) 提供后勤、生物标志物、生物统计、生物信息学和生物样本库支持来支持这一使命这使得 GTN 团队的研究人员能够优化 GBM 患者的 6-硫代-dG 治疗，以及 2) 通过使更广泛的网络能够访问相同的专业知识和组织，作为其他 GTN 站点的资源。 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-thio-dG 的早期临床试验，通过标准化组织收集方案和集中分析患者资格和肿瘤对 6-thio-dG 治疗反应的关键生物标志物（目标 1）。我们将通过对先前切除的肿瘤进行集中审查来提供专家神经病理学咨询使用 CLIA 批准的检测确定 IDH1/2 和 TERT 启动子突变状态，以确定是否有资格接受 6-thio-dG 治疗和肿瘤切除后，Bio-MIR Core 将再次进行监督。中枢神经病理学审查和测量药效学终点，包括 DNA 的 γH2AX 测量 Bio-MIR 核心将为收集、处理提供生物样本库服务将所有 GBM 患者组织储存在 CAP 认证的环境中，并将这些组织分发到杜克/UTSW GTN 和所有 GTN 站点（目标 2） Bio-MIR 核心还将提供生物统计和数据。用于进行、分析和报告相关研究并确保数据完整性的生物信息学专业知识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 核心将促进模范研究文化和最佳数据管理实践整个过程中使用以确保研究结果的数据完整性、来源、安全性和可重复性。 MIR Core 将受益于机构和 NIH 对关键共享资源（包括临床）的投资数据仓库和多机构生物样本库和样本共享，并利用三十多年来进行多中心 GBM 研究的研究人员。将促进 GTN 研究人员之间的合作，并将与指定网络合作跨GTN资源共享和参与先进疗法临床试验协调中心通过这种方式，Bio-MIR 核心将作为 GTN 指导委员会的多中心评估。不可或缺的资源，有助于实现 GTN 开发新颖、有效的药物的总体目标跨越血脑屏障并在诊所进行测试，以改善成人 GBM 的治疗。