Liquid biopsy of the lung to profile lung cancer

肺部液体活检以分析肺癌

基本信息

批准号：
10259860
负责人：
A McGarry Houghton
金额：
$ 25.9万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10259860
关键词：
Affect Attention Biological Assay Biological Markers Biopsy Blood Bronchoalveolar Lavage Bronchoalveolar Lavage Fluid Bronchoscopy Cancer Biology Cancer Patient Caring Cell Culture Techniques Cell Therapy Cells Cellular Assay Chest wall structure Clinic Clinical Clinical Trials Collection Companions Cryopreservation Cytology DNA Data Detection Diagnosis Diagnostic Enrollment Epidermal Growth Factor Receptor Exposure to Flow Cytometry Fred Hutchinson Cancer Research Center Genes Genome Genomics Goals Gold Health Care Costs Immune Immunogenomics Immunology Immunophenotyping Immunotherapy Integration Host Factors Irrigation Knowledge Laboratories Liquid substance Lung Lung Adenocarcinoma Lung Inflammation Lung Neoplasms Lymphocyte Malignant neoplasm of lung Measures Medicine Methods Modernization Molecular Molecular Analysis Molecular Profiling Morbidity - disease rate Mutation Needles Observational Study Outcome Patients Physicians Plasma Procedures Proteins Protocols documentation Provider Recovery Reporting Reproducibility Research Personnel Resected Sampling Specialized Program of Research Excellence Standardization Structure Survival Rate T cell receptor repertoire sequencing T-Lymphocyte T-cell receptor repertoire Techniques Time Tissue Sample Tissues Tumor Biology Tumor Markers Tumor Tissue Tumor-Derived Variant Work base biobank cancer biomarkers cancer diagnosis cancer genome cancer therapy cell dimension cell free DNA cell type clinical practice clinically relevant design early phase clinical trial exhaust experimental study first-in-human high dimensionality innovation liquid biopsy mortality novel optimal treatments patient population research study specific biomarkers statistics success targeted treatment tool treatment planning tumor tumor behavior tumor heterogeneity tumor microenvironment

项目摘要

PROJECT SUMMARY/ABSTRACT A tumor biopsy is traditionally performed for lung cancer diagnosis using either bronchoscopy through the airway or a needle aspiration through the chest wall. Advances in targeted and immune therapies now often require more tissue for molecular and immune profiling to optimally manage lung cancer. The yield for cancer diagnosis using modern bronchoscopic tools approaches only 50% across the spectrum of lung tumors biopsied, and the additional requirement for molecular and immune profiling erodes this yield further. This leads to delayed and suboptimal care, increased healthcare costs, and increased patient morbidity since patients can often require multiple procedures to obtain the correct information for treatment. Our group has recently demonstrated that targeted Bronchoalveolar Lavage (BAL) – or a washing of the lung cancer performed during a procedure – is a reservoir of genomic and cellular biomarkers in the lung tumor macroenvironment (TMaE). Further, we have demonstrated that molecular analyses of BAL from the lung TMaE recapitulate cancer biology in the lung tumor microenvironment (TMiE). While BAL is very safe and routinely performed during bronchoscopy, to date, it is a pauci-cellular fluid that is of limited clinical utility for cancer diagnosis. Beyond cytology that is low yield, there are no molecular or cellular assays that are used in the clinic to fully inform providers who treat lung cancer. Because of this, rigorous attention to how methods of collection, patient host factors and processing of BAL will alter genomic and high dimensional cell based assays is lacking. Our central hypothesis is: BAL globally samples the tumor microenvironment (TMiE) to overcome limitations of tumor heterogeneity and is more sensitive than blood for immunogenomic profiling due to increased quantities of tumor specific biomarkers. To realize our goal and prove our hypothesis, in depth analysis of the conditions affecting BAL for high dimensional genome and cell assays is required. Here, we propose studying how basic conditions in the lung, variations in acquisition of BAL, and storage and processing of BAL affect its utility for comprehensive genome profiling and analysis of the T cell repertoire. Following identification of key pre-analytic variables, we propose a standard operating procedure for implementation in observational biomarker and first-in-man clinical trials to demonstrate the clinical utility of our approach. Proposal success will facilitate the introduction of novel molecular assays into the clinic that augment extant and developing blood and tumor assays. This approach will be particularly relevant as we move into the era of precision guided therapies for lung cancer treatment, which have begun to reduce mortality in even the most advanced stages, over the coming years and decades.

项目摘要/摘要传统上，使用任何支气管镜检查通过气道进行肿瘤活检进行肺癌诊断或穿过胸壁的针头抽吸。靶向和免疫疗法的进步通常需要用于分子和免疫分析的更多组织，可最佳地管理肺癌。癌症诊断的产量使用现代支气管镜工具，在整个肺部肿瘤中仅使用50％的方法，分子和免疫谱分析的其他要求进一步产生。这导致延迟，由于患者通常需要多个程序以获取正确的治疗信息。我们的小组最近证明了有针对性的支气管肺泡灌洗（BAL）或手术过程中进行的肺癌的洗涤是一种肺肿瘤宏观环境（TMAE）中基因组和细胞生物标志物的储层。此外，我们还有证明对肺TMAE的BAL的分子分析在肺肿瘤中概括了癌症生物学微环境（TMIE）。虽然BAL非常安全且在支气管镜检查期间进行常规执行，但这是一个对癌症诊断的临床实用性有限的Pauci细胞液。除了低产量的细胞学外，没有诊所中使用的分子或细胞测定法，以完全告知治疗肺癌的提供者。因此，严格关注收集方法，患者宿主因素和BAL的处理方式将如何缺乏改变基因组和高维细胞测定法。我们的中心假设是：BAL在全球范围内样品肿瘤微环境（TMIE）克服肿瘤异质性的局限性，更多由于肿瘤特异性的数量增加而比血液敏感的免疫原状分析生物标志物。实现我们的目标并证明我们的假设，深入分析影响BAL的条件需要高维基因组和细胞测定。在这里，我们建议研究如何基本条件肺，BAL的获取的变化以及BAL的存储和处理影响其实用性，以综合 T细胞库的基因组分析和分析。识别关键的预分析变量后，我们建议在观察性生物标志物和人类临床上实施的标准操作程序试验以证明我们方法的临床实用性。提案成功将有助于引入小说分子测定到诊所，增强并发展出血液和肿瘤分析。这种方法会当我们进入肺癌治疗精确的指导疗法时代时，特别重要在未来几年和几十年中，即使是最先进的阶段，也已经开始降低死亡率。