Single Circulating Vesicle Analysis for Early Cancer Detection

用于早期癌症检测的单循环囊泡分析

基本信息

批准号：
9913496
负责人：
RALPH WEISSLEDER, MD, PHD
金额：
$ 21.92万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-12 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9913496
关键词：
Address Age Bar Codes Biological Markers Biology Cells Clinical Clinical Trials DNA Detection Disease EPHA2 gene Early Diagnosis Emerging Technologies Epidermal Growth Factor Receptor Evaluation Funding Glass Goals Gold Heterogeneity Individual Infrastructure Kinetics Lesion Light MSLN gene MUC5AC gene Malignant - descriptor Malignant Neoplasms Malignant neoplasm of pancreas Measurement Measures Methods Microfluidic Microchips Mucin 1 protein Mutate Operative Surgical Procedures Patients Periodicity Pharmaceutical Preparations Proteins Recurrent disease Reproducibility Resectable Residual Tumors Resolution Sampling Screening for cancer Signal Transduction Slide Source Specimen Techniques Technology Testing Time Vesicle Yang anticancer research base cancer biomarkers cancer type clinical practice cost effective experimental study extracellular vesicles improved innovation insight interest novel novel therapeutics pancreatic cancer patients patient response point of care prospective protein biomarkers protein profiling response thrombospondin 2 tumor tumor heterogeneity

项目摘要

Analysis of circulating extracellular vesicles (EV) have advanced over the last several years but challenges remain to reproducibly analyze samples in a clinical setting. If more sensitive and reproducible methods could be established, they would have far reaching applications in early cancer detection, measuring patient response to drugs, understanding tumor heterogeneity and discriminating different diseases. The problem is potentiated in pancreatic cancer (PDAC), where early detection methods are lacking, reproducibility of measurements has been a problem and an understanding of vesicle heterogeneity is missing. Furthermore, most existing technologies rely on bulk measurements which are inherently less sensitive since markers of interest are diluted (Yang et al., 2017, Sci Transl Med, 9). The goal of this proposal is to explore a novel single EV analysis (SEA) method (Lee et al, 2018, ACSnano, in press) to shed light on tumor EV (TEV) biomarker composition in PDAC. Specifically, we propose to i) integrate the method with on-chip microfluidics for improved sample handling while adding a MAb-DNA barcoding step for signal amplification and multiplexing (aim 1) and ii) expand and test the approach for point-of-care analyses of TEV in clinical samples (aim 2). The proposed single vesicle method has the potential to transform PDAC cancer research and clinical practice. It will allow us to discover the make-up of TEV in clinical specimen with far reaching applications for early detection (analysis of rare proteins) and treatment t evaluation in different types of cancers.

在过去的几年中，循环外囊泡（EV）的分析已经进步保持在临床环境中可重复分析样品。如果可以使用更敏感和可重复的方法被建立，它们在早期癌症检测中的应用很远，测量患者对药物的反应，了解肿瘤异质性并区分不同的疾病。问题是在缺乏早期检测方法的胰腺癌（PDAC）中增强测量已经是一个问题，对囊泡异质性的理解缺失。此外，大多数现有技术都依赖于批量测量，这些测量本质上对兴趣被稀释（Yang等，2017，Sci Transl Med，9）。该提议的目的是探索一个新颖的单曲 EV分析（SEA）方法（Lee等，2018，Acsnano，印刷中），以阐明肿瘤EV（TEV）生物标志物 PDAC中的组成。具体而言，我们建议i）将方法与芯片上的微流体进行改进样品处理同时添加mab-DNA条形码步骤，以进行信号扩增和多重（AIM 1）和II）扩展和测试临床样品中TEV的即时分析方法的方法（AIM 2）。提出的单曲囊泡方法有可能改变PDAC癌症研究和临床实践。它可以让我们发现 TEV在临床标本中的构成，并具有远达到早期检测的应用（稀有蛋白质分析）以及在不同类型的癌症中评估。