Point-of care Microfluidics for Early Detection of Cancer

 描述(申请人提供)：早期癌症检测不仅在为绝大多数实体恶性肿瘤提供根治疗法和防止死亡方面至关重要，而且还可以降低发病率和成本。然而，大多数现有的早期检测策略都存在较低的特异性：它们与在早期阶段识别真实癌症一样可能导致非浸润性癌症的假阳性或过度诊断而导致并发症和死亡。来自我们自己的小组和其他人的最新数据表明，循环中的肿瘤细胞(CTC)可能大量进入侵袭性但局限性的早期癌症患者的血流中。这些观察结果表明，在癌症的发展过程中，CTC的存在并非罕见的晚期事件，而可能是肿瘤血管侵犯的早期预兆，为最终建立可行的远处转移提供了相当长的一段时间。我们的具体战略是使用微流控CTC分离方法(CTC-iChip)结合数字液滴RNA(DdPCR)测量平台开发基于CTC中RNA的高灵敏度数字读数。值得注意的是，CTC-iChip是独一无二的，因为它没有关于肿瘤细胞类型的先验假设，因此它适用于所有癌症。在非侵袭性获取的肿瘤细胞中检测肿瘤谱系特异性RNA是最有可能是最具特异性和敏感性的技术，也是最有可能普遍用于早期检测侵袭性癌症的技术。为此，我们有三个截然不同但相互关联的目标。在目标一中，我们将CTC-iChip与数字液滴聚合酶链式反应相结合，开发出一种高度特异和灵敏的RNA-iChip。在AIM II中，我们将选择两种目前可用于敏感但非特异性筛查测试的癌症：前列腺癌和肺癌，我们建议使用RNA-iChip将这些测试转变为可靠的测试，从而能够对侵袭性和可治愈癌症进行广泛筛查。在AIM III中，我们建议开发护理点RNA-iChip，将其广泛传播到学术医疗中心以外的地方医院、肿瘤学诊所和医生办公室。前列腺癌和肺癌的成功将对降低癌症发病率和死亡率产生深远影响，并为广泛早期发现多种癌症开辟道路。

 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.