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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.

循环细胞外囊泡（EV）的分析在过去几年中取得了进展，但仍存在挑战