Nanotechnologies for Comprehensive Single Cancer Cell Analysis

用于综合单癌细胞分析的纳米技术

基本信息

批准号：
8726314
负责人：
STEPHEN R QUAKE
金额：
$ 49.66万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8726314
关键词：
Affinity Aftercare Ascites Asses Biological Biological Assay Biological Markers Bioreactors Blood Blood Circulation CCNE1 gene Cancer Center Cancer cell line Cell Count Cell secretion Cell surface Cells Cetuximab Characteristics Charge Chemicals Chromosome Deletion Clinical Collaborations Collecting Cell DNA Data Analyses Detection Development Devices Doxorubicin Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Exons Fluorescence Gene Expression Gene Proteins Genes Genetic Heterogeneity Genetic Transcription Genome Genomics Germ Cells Growth Heterogeneity Human Immunoglobulin Fragments Implant Individual Inhibitory Concentration 50 Introns Knowledge Label Life Liquid substance Malignant Neoplasms Malignant neoplasm of lung Measurement Measures Messenger RNA Methods Microfluidics Modeling Molecular Molecular Analysis Monitor Mus Mutation Nanotechnology Neoplasm Circulating Cells Outcome Paclitaxel Patients Phenotype Physiologic pulse Pleural effusion disorder Population Proteins Protocols documentation Qualifying RNA Raman Spectrum Analysis Reagent Reproducibility Resistance Sampling Sedimentation process Self-Sustained Sequence Replication Series Single Nucleotide Polymorphism Surface Technology Testing Time Transcript Translations Treatment Protocols Validation assay development base biophysical properties cancer cell cantilever data integration deletion analysis density falls genetic analysis genome analysis mRNA Expression nanofluidic nanolitre neoplastic cell oncology operation physical science resistance mechanism response single cell analysis therapeutic target tumor

项目摘要

Project Overview: Cancer therapeutics targeted against the Epidermal Growth Factor Receptor (EGFR) have demonstrated great potential in lung cancer; however, these agents are effective in only a subset of patients. Furthermore, tumors tliat are initially responsive frequently acquire resistance over time. Though it is straightforward to measure molecular (DNA, RNA, protein) and biophysical (mass, density, charge) characteristics of tumors in bulk, recent studies have shown wide cell-tocell variability and the importance of characterizing that variability in estimating patient outcome^^^. We hypothesize that molecular and biophysical characterizations of circulating cells can discriminate cells that are responsive to therapy from those that are resistant. When analyzing cells collected from the circulation, or from other bodily fluids (e.g., pleural effusions, ascites), typically only a small number of cells are available. To asses the cell-to-cell heterogeneity of this limited number of cells, ive propose to develop and to apply quantitative, comprehensive single-cell analysis devices for assessing the DNA genome (e.g., single nucleotide polymorphisms, fusions, deletions), RNA expression, protein abundance (cell surface, intracellular, and secretome abundance), and biophysical properties of single cells for the dual purposes of predicting a patient's likely response to EGFR-targeted therapies and for monitoring a patient's acquisition of resistance to EGFR-targeted therapies (Fig. N3.3.1). We propose two specific aims for the development, testing, and application of our comprehensive analysis platform (Table N3.3.1).

项目概述：针对表皮生长因子受体的癌症治疗（EGFR）在肺癌方面已显示出巨大潜力；然而，这些药物仅对一小部分有效的患者。此外，肿瘤最初有反应，随着时间的推移经常获得耐药性。虽然它可以直接测量分子（DNA、RNA、蛋白质）和生物物理（质量、密度、电荷）大量肿瘤的特征，最近的研究表明广泛的细胞间变异性以及表征该变异性在估计患者结果中的重要性^^^。我们假设循环细胞的分子和生物物理特征可以区分对治疗有反应的细胞和耐药细胞。当分析从循环系统或其他体液（例如胸腔积液、腹水）收集的细胞时，通常只有少量细胞可用。为了评估有限数量细胞的细胞间异质性，我建议开发并应用定量、全面的单细胞分析装置来评估 DNA 基因组（例如，单核苷酸多态性、融合、缺失）、RNA 表达、蛋白质丰度（细胞表面、细胞内和分泌体丰度）和单细胞的生物物理特性，用于预测患者对 EGFR 靶向治疗的可能反应的双重目的以及监测患者对 EGFR 靶向治疗产生耐药性的情况（图 N3.3.1）。我们为我们的综合分析平台的开发、测试和应用提出了两个具体目标（表N3.3.1）。