Molecular Detection and Profiling of Circulating Tumor Cells

循环肿瘤细胞的分子检测和分析

• 批准号: 7800765
• 负责人: Jered Brackston Haun
• 金额: $ 4.42万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-05-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7800765
• 关键词: Address; Antineoplastic Agents; Biological Markers; Biological Process; Biological Sciences; Biopsy; Blood; Blood specimen; Caliber; Cancer cell line; Cell Count; Cell Separation; Cells; Clinical; Cytokeratin; Detection; Development; Devices; Diagnostic; Differentiation Antigens; Disease; Disease Progression; Epidermal Growth Factor Receptor; Epithelial; Evaluation; Family; Goals; Grant; Human; Human body; Incidence; Ions; Lasers; Lateral; Leukocytes; Localized Malignant Neoplasm; Magnetic Resonance; Magnetic Resonance Imaging; Magnetism; Malignant Neoplasms; Measurement; Medical; Medicine; Methods; Microfluidics; Molecular; Molecular Analysis; Molecular Target; Monitor; Nanotechnology; Patients; Pattern; Peripheral; Primary Neoplasm; Procedures; Process; Proteins; Reading; Recovery; Research; Resolution; Ribosomal Protein S6; Sampling; Science; Sensitivity and Specificity; Signal Transduction; Silicon; Site; Specimen; Staging; Stream; System; TACSTD2 gene; Techniques; Technology; Temperature; Therapeutic; Time; Tumor Expansion; Whole Blood; Work; base; cancer cell; cancer diagnosis; cancer therapy; drug development; extracellular; molecular phenotype; multidisciplinary; nanoparticle; neoplastic cell; novel; outcome forecast; peripheral blood; prototype; rapid detection; research study; response; sensor; treatment response; treatment strategy; tumor; validation studies

DESCRIPTION (provided by applicant): The long-term goal of the proposed research is to develop a novel sensor device platform that is capable of detecting and molecularly profiling circulating tumor cells (CTCs) in clinical samples. CTCs are rare cancer cells that have escaped from a primary tumor site and entered the blood stream. They have been identified in the peripheral blood of most patients with metastatic disease as well as in patients with localized cancers, but at exceedingly low levels (approximately 1-100 cells per ml of blood). It is our hypothesis that these peripheral cells can be used for molecular analysis, which could non-invasively provide valuable information for use in prognosis evaluation, anticancer-drug development, and ultimately, personalized cancer therapy based on CTCs. To date, the technology required to molecularly characterize these cells is lacking because existing clinical technologies are too insensitive. In prior research, our lab developed a prototype micro- NMR (p-NMR) sensor chip that has been used to detect cancer cells that are specifically tagged with superparamagnetic nanoparticles. This technique has been termed diagnostic magnetic resonance (DMR), In this proposal 1 seek to significantly advance DMR technology so that it may be applied in clinical use for molecular detection and profiling of CTCs. To achieve this goal, DMR detection sensitivity and specificity will be dramatically increased through the following aims: Aim 1. Extensively optimize the procedures used to tag tumor cells with magnetic nanoparticles targeted to intracellular and extracellular molecular biomarkers, and Aim 2. Develop an integrated microfluidics component that isolates CTCs from other cells in the blood based on size and delivers them directly to the p-NMR sensor. This work represents a multidisciplinary effort that calls on components from the fields of nanotechnology, molecular targeting, magnetic resonance imaging/sensing, and microfluidics to develop a novel device platform capable of interrogating clinical CTC samples, which could enable real-time molecular analysis of tumor samples and facilitate rational treatment decisions in an era where molecularly targeted therapies are emerging. The proposed research has broad applications for studying human cancer cells that are obtained from blood samples, Information could thus be obtained non-invasively to evaluate patient prognosis, devise treatment strategies, and monitor therapeutic response.

描述（由申请人提供）：拟议研究的长期目标是开发一种新型传感器设备平台，能够检测和分子分析临床样本中的循环肿瘤细胞（CTC）。CTC是从原发肿瘤部位逃逸并进入血流的罕见癌细胞。它们已在大多数转移性疾病患者以及局部癌症患者的外周血中被鉴定，但水平极低（约1-100个细胞/ml血液）。我们的假设是，这些外周细胞可用于分子分析，这可以非侵入性地提供有价值的信息，用于预后评估，抗癌药物开发，并最终基于CTC的个性化癌症治疗。到目前为止，缺乏对这些细胞进行分子表征所需的技术，因为现有的临床技术太不敏感。在之前的研究中，我们的实验室开发了一种原型微NMR（p-NMR）传感器芯片，该芯片已用于检测用超顺磁性纳米颗粒特异性标记的癌细胞。该技术被称为诊断磁共振（DMR）。在该提案中，I寻求显著地推进DMR技术，使得其可以应用于临床应用中，用于CTC的分子检测和分析。为了实现这一目标，DMR检测的灵敏度和特异性将通过以下目标显着提高：目标1。广泛优化用于用针对细胞内和细胞外分子生物标志物的磁性纳米颗粒标记肿瘤细胞的程序，以及Aim 2。开发一种集成的微流体组件，根据大小将CTC与血液中的其他细胞分离，并将其直接输送到p-NMR传感器。这项工作代表了一项多学科的努力，呼吁来自纳米技术，分子靶向，磁共振成像/传感和微流体领域的组件开发一种能够询问临床CTC样本的新型设备平台，这可以实现肿瘤样本的实时分子分析，并在分子靶向治疗正在出现的时代促进合理的治疗决策。这项研究在研究从血液样本中获得的人类癌细胞方面具有广泛的应用，因此可以非侵入性地获得信息，以评估患者预后，制定治疗策略和监测治疗反应。