Point-of care Microfluidics for Early Detection of Cancer

 描述（由申请人提供）：早期癌症检测不仅在为绝大多数实体恶性肿瘤提供治愈性治疗和预防死亡方面至关重要，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特异性差的问题：它们很可能因假阳性或非侵入性癌症的过度诊断而导致并发症和死亡，因为它们在早期阶段识别出真正的癌症。来自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）可能会大量脱落到患有侵袭性但局部和早期癌症的患者的血流中。这些观察结果表明，CTC的存在可能是肿瘤血管浸润的早期预兆，而不是癌症演变中的罕见和晚期事件，在最终建立可行的远处转移之前的相当长的一段时间内。我们的具体策略是使用微流体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的高度灵敏的数字读出。值得注意的是，CTC-iChip的独特之处在于它没有对肿瘤细胞的类型进行先验假设，因此它适用于所有癌症。在非侵入性获取的肿瘤细胞内检测肿瘤谱系特异性RNA是最有可能不仅高度特异性和灵敏度而且对于侵袭性癌症的早期检测是通用的技术。为此，我们有三个不同但相互关联的目标。目的一：将CTC-iChip与数字微滴PCR技术相结合，开发出一种高特异性、高灵敏度的RNA-iChip。在Aim II中，我们将选择两种目前可用的敏感但非特异性筛选测试的癌症，前列腺癌和肺癌，我们建议使用RNA-iChip将其转化为强大而可靠的测试，从而能够广泛筛查侵袭性和可治愈的癌症。在目标III中，我们建议开发护理点RNA-iChip广泛传播，超越学术医疗中心，到当地医院，肿瘤诊所和医生办公室。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，并为多种癌症的广泛早期检测开辟道路。

 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.