Liquid biopsy of the lung to profile lung cancer

肺部液体活检以分析肺癌

• 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
• 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

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.

项目概要/摘要 传统上使用支气管镜检查通过气道进行肿瘤活检以诊断肺癌 或通过胸壁进行针吸。靶向和免疫疗法的进步现在通常需要 更多组织用于分子和免疫分析，以最佳地管理肺癌。癌症诊断率 使用现代支气管镜工具只能对 50% 的肺部肿瘤进行活检，而且 对分子和免疫分析的额外要求进一步削弱了这一产量。这会导致延迟和 护理欠佳、医疗费用增加以及患者发病率增加，因为患者经常需要 多次程序以获得正确的治疗信息。我们的小组最近证明了 靶向支气管肺泡灌洗 (BAL) – 或手术过程中对肺癌进行的清洗 – 是一种 肺肿瘤宏观环境（TMaE）中的基因组和细胞生物标志物库。进一步，我们有 证明来自肺 TMaE 的 BAL 的分子分析概括了肺肿瘤中的癌症生物学 微环境（TMiE）。虽然 BAL 非常安全并且通常在支气管镜检查期间进行，但迄今为止，它是一种 寡细胞液，对于癌症诊断的临床用途有限。除了低产量的细胞学之外，还有 临床上没有使用任何分子或细胞测定来充分告知治疗肺癌的提供者。 因此，严格关注 BAL 的收集方法、患者宿主因素和处理将如何 缺乏改变基因组和高维细胞的测定。我们的中心假设是：全球 BAL 对肿瘤微环境（TMiE）进行采样以克服肿瘤异质性的局限性，并且更 由于肿瘤特异性数量增加，免疫基因组分析比血液敏感 生物标志物。为了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分析。在这里，我们建议研究一下 肺、BAL 采集的变化以及 BAL 的存储和处理会影响其综合用途 T 细胞库的基因组分析和分析。在确定了关键的预分析变量之后，我们 提出用于观察生物标志物和首次人体临床实施的标准操作程序 试验来证明我们的方法的临床实用性。提案的成功将有助于引入新颖的 将分子检测引入临床，增强现有和正在开发的血液和肿瘤检测。这种方法将 随着我们进入肺癌治疗的精准引导疗法时代，这一点尤其重要。 在未来几年和几十年里，即使是在最晚期阶段，死亡率也开始降低。