In-patient hospice and rapid autopsy to interrogate tumor heterogeneity

住院临终关怀和快速尸检以询问肿瘤异质性

• 批准号: 8763591
• 负责人: Udayan Guha
• 金额: $ 12.75万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8763591
• 关键词: Area; Autopsy; Back; Biological Assay; Biological Markers; Cancer Etiology; Cell Line; Cessation of life; Chest; Clinical; Clinical Protocols; Clonal Evolution; Core Biopsy; Disease; Family member; Frequencies; Genomics; Goals; Heterogeneity; Home environment; Hour; Institutional Review Boards; Investigation; Knowledge; Malignant Neoplasms; Malignant neoplasm of lung; Mass Spectrum Analysis; Medical Oncology; Mesothelioma; Mutation; Nature; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Outcome; Patients; Primary Neoplasm; Process; Proteins; Proteomics; Protocols documentation; Reagent; Sampling; Site; Thymus Epithelial Neoplasm; Tissue Procurements; Tissues; Tumor Biology; Tumor Tissue; Writing; base; deep sequencing; hospice environment; insight; neoplastic cell; next generation sequencing; novel; resistance mechanism; tumor; tumor progression

We wrote this clinical protocol this year. This was reviewed in the Concept and full protocol reviews by the Medical Oncology Branch and Affiliates' clinical protocol review process. Finally this was approved by the IRB couple of months back. We have identified couple of patients who are on home hospice now. We have initiated discussions with those patients and family members to explain this protocol. Tissue procurement by rapid autopsies provides an effective way to investigate tumor biology of primary and a broad range of metastatic sites in a manner not possible by any other means. In addition to tumor heterogeneity, tissue obtained at autopsy could yield important biologic insights into frequency and nature of secondary mutations associated with tumor progression, novel biomarkers and mechanisms of resistance to treatment. The full extent and consequences of tumor heterogeneity can be evaluated by deep sequencing and global analysis of genetic alterations at the protein level of simultaneous core biopsies from several areas of the primary tumor and metastases and correlation with clinical outcome. To our knowledge, no such studies have been done in NSCLC. We intend to collect tumor tissue from up to ten different sites of metastatic disease to study inter-tumor heterogeneity. Up to six different cores from each site will be stored properly to interrogate intra-tumor heterogeneity. Next generation sequencing and in-depth mass spectrometry-based proteomics analyses will be performed on these samples to assay tumor heterogenety. We will also attempt to generate cell lines from several sites from a patient that are expected to be unique reagents to study tumor heterogenety and tumor biology.

我们今年写了这份临床方案。医学肿瘤学分会及其附属机构的临床方案审查流程在概念和完整方案审查中对此进行了审查。最后，几个月前，IRB 批准了这一计划。我们已经确定了几名目前正在家庭临终关怀中心接受治疗的患者。我们已开始与这些患者和家属进行讨论，以解释该方案。通过快速尸检获取组织提供了一种有效的方法来研究原发性和广泛转移部位的肿瘤生物学，这是任何其他方法都无法实现的。除了肿瘤异质性之外，尸检获得的组织还可以对与肿瘤进展相关的二次突变的频率和性质、新的生物标志物和治疗耐药机制产生重要的生物学见解。肿瘤异质性的全部范围和后果可以通过对来自原发肿瘤和转移的多个区域的同时核心活检的蛋白质水平的遗传改变进行深度测序和全局分析以及与临床结果的相关性来评估。据我们所知，尚未在非小细胞肺癌中进行此类研究。我们打算从多达十个不同的转移性疾病部位收集肿瘤组织，以研究肿瘤间的异质性。每个位点最多六个不同的核心将被正确存储，以询问肿瘤内的异质性。将对这些样本进行下一代测序和基于深入质谱的蛋白质组学分析，以测定肿瘤异质性。我们还将尝试从患者的多个位点生成细胞系，这些细胞系有望成为研究肿瘤异质性和肿瘤生物学的独特试剂。