Development of Technologies for Rapid Isolation and Genome Sequencing of Single Circulating Tumor Cells in Prostate Cancer

绝大多数癌症死亡是由转移引起的，也就是癌症从身体的一个部位扩散到另一个部位。为了让癌症扩散，被称为循环肿瘤细胞的细胞必须从肿瘤中分离出来，在血液中循环，然后重新附着到不同的组织上。因此，循环中的肿瘤细胞被认为是转移的媒介，可能被用来评估每个患者癌症的遗传基础以及他们对潜在治疗的反应。循环肿瘤细胞的遗传分析目前受到血流中这些细胞的极端稀有以及单个细胞之间的差异的限制。该项目旨在通过开发一种快速分离单个循环肿瘤细胞进行基因组测序的技术来应对这一挑战。然后，我们将通过分离和测序目前正在进行相关临床研究的晚期前列腺癌患者的单个循环肿瘤细胞来测试这项技术。然后将来自单个循环肿瘤细胞的基因组序列与其他可用的数据进行比较，以确定其在诊断和治疗中的价值。基因组测序已经在一些癌症中被用来预测患者对某些药物的反应。该项目将开发一种技术来分离和测序与转移最相关的细胞，这将为医生提供更好的信息来评估每个患者的疾病，以便设计出个性化的治疗计划。

The vast majority of cancer deaths are caused by metastasis, or the spread of cancer fromone part of the body to another. In order for cancer to spread, cells known as circulating tumorcells, must detach from a tumor, circulate in the bloodstream, and reattach to a differenttissue. Therefore, circulating tumor cells are considered to be the agents of metastasis thatcould potentially be used to evaluate the genetic basis of each patients cancer and how theymight respond to potential treatments. Genetic analysis of circulating tumor cells is currentlylimited by the extreme rarity of these cells in the bloodstream, as well as by the differencesacross individual cells. This project aims to address this challenge by developing a technologyto rapidly isolate individual circulating tumor cells for genome sequencing. We will then testthis technology by isolating and sequencing single circulating tumor cells from patients withadvanced prostate cancer who are currently enrolled in related clinical studies. The genomesequence from single circulating tumor cells will then be compared with other available data inorder to determine its value in diagnosis and treatment. Genome sequencing is already beingused in some cancers to predict how patients will respond to certain drugs. This project willdevelop a technology to isolate and sequence cells that are most relevant to metastasis,which will give physicians significantly better information to evaluate each patients disease inorder to devise a personalized treatment plan.