Point-of care Microfluidics for Early Detection of Cancer

用于癌症早期检测的护理点微流控

• 批准号: 8999413
• 负责人: Daniel A. Haber
• 金额: $ 172.16万
• 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: 2010-09-30 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8999413
• 关键词: Academic Medical Centers; Address; Biological; Biological Assay; Biological Markers; Biomedical Engineering; Blood; Blood Cells; Cancer Biology; Cancer Patient; Cancer cell line; Care Technology Points; Cell Extracts; Cell Separation; Cessation of life; Chemicals; Clinic; Complement; Complementary DNA; Complex; Cytolysis; Data; Decision Making; Detection; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Distant Metastasis; Early Diagnosis; Early treatment; Enrollment; Evaluation; Event; Evolution; Funding Mechanisms; Goals; Hospitals; Human; Individual; Lung; Lung nodule; Magnetism; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Measurement; Mechanics; Microfluidics; Molecular; Moon; Morbidity - disease rate; Neoplasm Circulating Cells; Noise; Oncologist; Optics; Patient Care; Patients; Physicians' Offices; Process; Prostate; Quality of Care; RNA; RNA Sequences; RNA analysis; RNA marker; Reagent; Research Personnel; Screening for cancer; Sensitivity and Specificity; Series; Side; Signal Transduction; Solid; Specificity; Specimen; Staging; Stream; System; Technology; Testing; Time; Transcript; Tumor Vascular Invasion; Uncertainty; Validation; Whole Blood; Work; base; cancer care; cancer cell; cancer diagnosis; cancer genetics; candidate marker; clinical care; cost; differential expression; digital; empowered; high risk; improved; low-dose spiral CT; men; mortality; multidisciplinary; neoplastic cell; oncology; personalized cancer care; point of care; prevent; programs; public health relevance; quantum; screening; serum PSA; standardize guidelines; success; technological innovation; transcriptome sequencing; tumor

 DESCRIPTION (provided by applicant): Early cancer detection is not only critical in providing curative therapies for the vast majority of solid malignancies and preventing mortality, but also reducing morbidity and costs. However, most existing strategies for early detection suffer from poor specificity: they are as likely to cause complications and deaths from false positives or overdiagnosis of non-invasive cancers as they are from identifying true cancers at an early stage. Recent data from our own group and others show that Circulating Tumor Cells (CTCs) may be shed in significant numbers into the blood stream of patients with invasive but localized and early-stage cancers. These observations suggest that, rather than being a rare and late event in the evolution of cancer, the presence of CTCs may be an early herald of tumor vascular invasion, preceding a considerable period of time for the eventual establishment of viable distant metastases. Our specific strategy is to develop a highly sensitive digital readout based on RNA in CTCs using the microfluidic CTC isolation approach (CTC-iChip) combined with digital droplet RNA (ddPCR) measurement platform. It is important to note that the CTC-iChip is unique in that it makes no a priori assumption about the type of the tumor cells and as such it applies to all cancers. Detecting tumor lineage specific RNA within noninvasively accessed tumor cells is the technology most likely to be not only highly specific and sensitive but also universal for early detection of invasive cancer. To this end, we have 3 distinct but interrelated Aims. In Aim I, we will integrate CTC-iChip and digital droplet PCR to develop a highly specific and sensitive RNA-iChip. In Aim II, we will select two cancers for which sensitive but nonspecific screening tests are currently available, prostate and lung cancer, and we propose to transform these into robust and reliable tests using RNA-iChip that would enable broad screening for invasive and curable cancers. In Aim III, we propose to develop the point of care RNA-iChip broad dissemination beyond academic medical centers to local hospitals, oncology clinics and to physicians' offices. Success with prostate and lung cancers would have a profound impact in decreasing cancer morbidity and mortality, and open a path toward broad-based early detection of multiple cancers.

 描述（由适用提供）：早期癌症检测不仅对于为绝大多数稳定恶性肿瘤提供治疗疗法至关重要，而且还可以降低发病率和成本。但是，大多数现有的早期检测策略都具有较差的特异性：它们可能导致虚假阳性或非侵入性癌症过度诊断的并发症和死亡，就像在早期识别真正的癌症所致。我们自己的小组和其他人的最新数据表明，循环肿瘤细胞（CTC）可能会大量流入侵入性但局部和早期癌症患者的血液中。这些观察结果表明，CTC的存在不是在癌症的演变中是罕见的后期事件，而是早期的肿瘤血管侵袭的先驱，在事件建立可行的远处转移酶之前已经有相当长的一段时间。我们的具体策略是使用微流体CTC隔离方法（CTC-ICHIP）与数字液滴RNA（DDPCR）测量平台相结合，开发基于CTC中RNA的高度敏感的数字读数。重要的是要注意，CTC-ICHIP是独一无二的，因为它没有对肿瘤细胞的类型进行先验假设，因此适用于所有癌症。检测非侵入性访问肿瘤细胞内肿瘤谱系特异性RNA是该技术最有可能不仅具有高度特异性和敏感性，而且还具有通用的侵入性癌症。为此，我们有3个不同但相互关联的目标。在AIM I中，我们将集成CTC-ICHIP和数字液滴PCR，以开发高度特异性和敏感的RNA-ICHIP。在AIM II中，我们将选择两种癌症，目前可以使用敏感但非特异性的筛查测试，即前列腺癌和肺癌，我们建议使用RNA-ICHIP将其转变为可靠和可靠的测试，以实现侵入性且可固化的可治愈癌症的广泛筛查。在AIM III中，我们建议将RNA-ICHIP的关注点扩展到学术医疗中心以外的广泛传播到当地医院，肿瘤学诊所和医师办公室。前列腺和肺癌的成功将对降低癌症发病率和死亡率产生深远的影响，并为多种癌症的早期发现开辟了道路。