Circulating Biomarker Core

项目总结/摘要 微创液体活检彻底改变了我们对癌症生物学的理解， 用于疾病监测和药物开发的生物标志物。对癌症进行纵向抽样的做法- 来自血液的衍生物质，包括循环肿瘤细胞（CTC）和循环肿瘤DNA（ctDNA）， 目前，只有少数具备必要技术能力的商业实体或学术实验室才能开展这一工作。的 UWCCC循环生物标志物核心（CBC）成立于2019年，利用创新技术， 临床研究基础设施，以扩大UWCCC成员获得这些生物标本和检测的机会， 直接涉及UWCCC战略计划A2.1。CBC的结构遵循NCI生物标志物指南 开发重点是检测试剂盒的稳健性、可行性和对探索性、综合性和整体性的影响 生物标记1. CBC拥有一个专家研究团队和设备来识别，组织和处理 来自临床试验患者的样本，无论是在UWCCC，跨流域，还是来自国家联盟。 纯化的标准分析物的范围从ctDNA、细胞因子、代谢物和外来体的血浆，以及 用于CTC分析和免疫细胞研究的有核细胞。所进行的分析包括罕见细胞表型， 基因表达谱和遗传分析等。CBC与翻译协调 科学生物核心（TSB）生物库和临床生物标本疾病导向团队（DOT）每周一次，以确保 有效和及时地处理这些小组收集的样品。与威斯康星州合作 卫生实验室，CBC现在提供了一个管道，将有前途的液体生物标志物推向CLIA认证 可以作为临床试验的生物标志物。一个项目，评估基因表达分析， 前列腺癌CTC（UH 2CA 260389;临床肿瘤学杂志2）已经进入这一管道，并且正在 作为一个完整的生物标志物和临床级检测开发。CBC为研究人员提供了访问 创新技术，开发新的生物标志物，并在临床试验中使用 建立了生物标本处理和分析的标准操作规程（SOP）。CBC由 专家教师领导人，包括CBC主任约书亚朗博士，UWCCC TM项目联合负责人，和詹妮弗博士 Schehr自CBC成立以来一直担任该公司的设施总监。我们的目标是：（1）发展 生物标志物的探索性液体活检，以促进我们对癌症和治疗抗性的理解; 2） 进行临床测试和翻译新的液体活检测定作为综合生物标志物，以及3）进行 临床诊断实验室实施准备中的分析验证， 生物标志物。在2019-2021年，CBC作为发展中的核心，对UWCCC成员产生了巨大的影响 research.具体来说，CBC与46个独立用户合作，其中67%是UWCCC成员， 5个科学项目，产生了6篇同行评审的出版物和14项临床试验。随着近期 随着CBC设施和专家网络的扩大，我们预计来年的影响会更大。

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.