权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

项目总结/文摘