Circulating Biomarker Core

循环生物标志物核心

• 批准号: 10626514
• 负责人: Joshua Michael Lang
• 金额: $ 3.13万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-25 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10626514
• 关键词: Address; Amendment; Basic Science; Biological Assay; Biological Markers; Blood; Blood specimen; Cancer Biology; Cells; Certification; Circulation; Clinical; Clinical Oncology; Clinical Research; Clinical Trials; Collaborations; Comprehensive Cancer Center; Core Facility; Data; Development; Diagnostic; Disease; Ensure; Equipment; Faculty; Funding; Gene Expression; Gene Expression Profiling; Genomics; Goals; Hygiene; Immune; Institution; Instruction; Investigation; Journals; Laboratories; Liquid substance; Malignant Neoplasms; Malignant neoplasm of prostate; Molecular; Monitor; Multi-Institutional Clinical Trial; Neoplasm Circulating Cells; Outcome; Patients; Peer Review; Phenotype; Plasma; Preparation; Procedures; Process; Prognostic Marker; Proteins; Publications; Reproducibility; Research; Research Infrastructure; Research Personnel; Review Committee; Sampling; Services; Strategic Planning; Structure; Technology; Testing; Training; Translating; Translational Research; Translations; Validation; Wisconsin; biobank; biomarker development; cell free DNA; circulating biomarkers; clinical care; clinical diagnostics; clinical translation; cytokine; drug development; exosome; genetic analysis; improved; innovation; innovative technologies; liquid biopsy; malignant breast neoplasm; member; minimally invasive; neoplastic cell; novel; novel marker; patient stratification; pharmacodynamic biomarker; predictive marker; programs; prospective; research clinical testing; resistance mechanism; therapy resistant; transcriptomics; treatment response; tumor DNA; validation studies

PROJECT SUMMARY/ABSTRACT Minimally invasive liquid biopsies have revolutionized our understanding of cancer biology and emerged as biomarkers for disease monitoring and drug development. The practice of longitudinal sampling of cancer- derived material from blood, including Circulating Tumor Cells (CTCs) and circulating tumor DNA (ctDNA), has been limited to a few commercial entities or academic laboratories with the requisite technological capacity. The UWCCC Circulating Biomarker Core (CBC) was established in 2019, leveraging innovative technologies and clinical research infrastructure, to expand access to these biospecimens and assays for UWCCC members, and directly addresses UWCCC strategic plan A2.1. The CBC is structured to follow NCI guidance for biomarker development focusing on assay robustness, feasibility, and impact for exploratory, integrated, and integral biomarkers1. The CBC houses an expert research team and equipment to identify, organize, and process samples from patients on clinical trials, both at UWCCC, across the catchment, and from national consortia. Standard analytes purified range from plasma for ctDNA, cytokines, metabolites, and exosomes as well as nucleated cells for CTC analysis and immune cell studies. The analyses performed include rare cell phenotyping, gene expression profiling, and genetic analysis among others. The CBC coordinates with the Translational Science Biocore (TSB) Biobank and clinical Biospecimen Disease-Oriented Team (DOT) weekly to ensure efficient and timely processing of samples collected by these teams. In collaboration with the Wisconsin State Lab of Hygiene, the CBC now provides a pipeline to move promising liquid biomarkers towards CLIA-certification that can serve as an integral biomarker for clinical trials. One project, evaluating gene expression analysis of prostate cancer CTCs (UH2CA260389; Journal of Clinical Oncology2), has entered this pipeline and is being developed as an integral biomarker and clinical grade assay. The CBC provides researchers access to innovative technology to develop new biomarkers as well as test these biomarkers in clinical trials using established standard operating procedures (SOPs) for biospecimen processing and analysis. The CBC is led by expert faculty leaders including CBC Director Dr. Joshua Lang, UWCCC TM program co-leader, and Dr. Jennifer Schehr who has served as facility director for the CBC since its inception. Our Specific Aims are to 1) develop exploratory liquid biopsy of biomarkers to advance our understanding of cancer and treatment resistance; 2) perform clinical testing and translation of new liquid biopsy assays as integrated biomarkers, and 3) perform analytical validation in preparation for clinical diagnostic laboratory implementation as integrated and integral biomarkers. Over 2019-2021 as a developing core, CBC has had tremendous impact on UWCCC member research. Specifically, CBC collaborated with 46 unique users, of which 67% were UWCCC members across five scientific programs, which resulted in 6 peer-reviewed publications and 14 clinical trials. With the recent expansion of CBC facilities and expert network, we anticipate even greater impact in the coming year.

项目摘要/摘要 微创的液体活检使我们对癌症生物学的理解彻底改变了，并成为 疾病监测和药物开发的生物标志物。癌症纵向采样的实践 源自血液，包括循环肿瘤细胞（CTC）和循环肿瘤DNA（CTDNA）的材料 仅限于具有必要技术能力的一些商业实体或学术实验室。这 UWCCC循环生物标志物核心（CBC）成立于2019年，利用创新技术和 临床研究基础设施，扩大对UWCCC成员的生物测量和测定的访问权限，以及 直接解决UWCCC战略计划A2.1。 CBC结构遵循NCI生物标志物指南 开发侧重于测定鲁棒性，可行性以及对探索性，集成和积分不可或缺的影响 生物标志物1。 CBC设有专家研究团队和设备，以识别，组织和处理 来自UWCCC的临床试验患者的样本，整个集水区和国家财团。 标准分析物纯化范围从ctDNA，细胞因子，代谢物和外泌体等等离子体以及 用于CTC分析和免疫细胞研究的成核细胞。进行的分析包括稀有细胞表型， 基因表达分析和遗传分析等。 CBC与翻译协调 科学生物库（TSB）生物库和临床生物传播疾病的团队（DOT）每周 这些团队收集的样品的有效及时处理。与威斯康星州合作 卫生实验室，CBC现在提供了一条管道，将有希望的液体生物标志物移至Clia-Centification 可以作为临床试验的整体生物标志物。一个项目，评估基因表达分析 前列腺癌CTC（UH2CA260389；临床肿瘤学杂志）已进入此管道，正在 作为整体生物标志物和临床等级测定法。 CBC为研究人员提供了访问 创新技术以开发新的生物标志物，并在临床试验中测试这些生物标志物 建立的标准操作程序（SOP），用于生物测量处理和分析。 CBC由 CBC主任Joshua Lang，UWCCC TM Program共同领导和Jennifer博士在内的专家教师领导人 Schehr自成立以来一直担任CBC的设施总监。我们的具体目的是1） 生物标志物的探索性液体活检，以提高我们对癌症和治疗耐药性的理解； 2） 作为集成生物标志物进行新的液体活检测定法进行临床测试和翻译，3）执行 分析验证，以准备临床诊断实验室实施，作为集成和积分 生物标志物。在2019 - 2021年作为发展中心，CBC对UWCCC成员产生了巨大影响 研究。具体而言，CBC与46个唯一用户合作，其中67％是UWCCC成员 五个科学计划，有6个经过同行评审的出版物和14项临床试验。与最近的 CBC设施和专家网络的扩展，我们预计来年会有更大的影响。