A blood test to identify prostate cancer patients at risk for visceral metastasis

项目摘要 R01提案的长期目标是开发一种基于循环肿瘤细胞的检测方法 识别有发生内脏转移风险的前列腺癌(PCA)患者 (Vm)。Posadas博士(雪松-西奈)和Tseng博士(CytoLumina)形成了一种独特的 面向该项目的功能性学术/产业合作伙伴关系。 转移性、去势抵抗前列腺癌(MCRPC)中的VM是一种新兴的、尚未解决的 有问题。患有VM的患者显著缩短了癌症特异性生存时间并死于 器官衰竭的方式与骨主性疾病患者截然不同。VM通常是 只有在器官功能已经受损的情况下才能在请求的成像中发现-通常是晚期 临床病程但影响超过45%的晚期PCa患者。早期治疗可以 改善结果，但这需要及时发现。因此，存在一种未得到满足的需求，即确定 患者面临VM定制成像监视的风险并创造机会进行更改 疾病轨迹。 循环肿瘤细胞(CTCs)是一种可以从全血中分离出来的罕见癌细胞。 纳米尼龙搭扣试验是由CytoLumina推出的一种新的细胞分离技术，即 能够识别少量血液中的CTCs(低至1毫升)。纳米尼龙搭扣的应用 检测导致了基于核形态的CTC亚群的鉴定，包括 直径小于8.5微米的核称为极小核CTCs(VSNCTCs)。我们有 研究发现，VSNCTCs的出现与男性PCa患者Vm的存在有关。 我们假设VSNCTC出现在通过常规方式可检测到的VM之前 MCRPC的放射学评估。这一假设将通过(目标1)的分析来检验 过去3年在我们的注释中连续收集的CTC样品 CTC/血库--这项工作的独特和宝贵资源，(目标2) 男性mCRPC患者的CTC分析我们的早期工作表明，vsnCTC出现在几个月前 通过传统成像技术可以检测到这些VM。 这一研究项目将为早期成像和治疗创造机会 可以改变患者的临床病程。作为副产品，这项工作将创造一个新的临床 通过识别有VM风险的男性，在PCA中留出空间。NanoVelcro vSnCTC检测将提供 简单、微创和经济高效的方法来识别mCRPC患者的风险 VM，从而允许医生对患者进行个性化的监控、治疗和治疗。

Project Summary The long-term goal of this R01 proposal is to develop a circulating tumor cell-based assay to identify prostate cancer (PCa) patients who are at risk for developing visceral metastasis (VM). Drs. Posadas (Cedars-Sinai) and Tseng (CytoLumina) have formed a unique and functional academic/industrial partnership geared toward this project. VM in metastatic, castration-resistant PCa (mCRPC) is an emerging and unaddressed problem. Patients with VM have significantly foreshortened cancer-specific survival and die from organ failure in a fashion distinct from patients with bone-predominant disease. VM are typically found on imaging requested only when organ function is already compromised-typically late in the clinical course but affect over 45% of patients with advanced PCa. Early treatment can improve outcome but this requires timely detection. Thus, there is an unmet need to identify patients at risk for VM to customize imaging surveillance and create an opportunity to alter disease trajectory. Circulating tumor cells (CTCs) are rare cancer cells that can be isolated from whole blood. The NanoVelcro assay is a novel cellular isolation technology introduced by CytoLumina that is capable of identifying CTCs in small volumes of blood (as little as 1 mL). Use of NanoVelcro assay has led to the identification of CTC subsets based on nuclear morphology including those with nuclei less than 8.5 µm in diameter called very small nuclear CTCs (vsnCTCs). We have found that the appearance of vsnCTCs is associated with the presence of VM in men with PCa. We hypothesize that vsnCTCs appear before the VM are detectable by conventional radiographic assessment in mCRPC. This hypothesis will be tested by (aim 1) an analysis of CTC samples that have been serially collected over the past 3 years in our annotated CTC/blood bank – a unique and invaluable resource for this work and, (aim 2) a prospective CTC analysis of men with mCRPC. Our early work shows that vsnCTCs appear months before the VM are detectable by conventional imaging techniques. This investigative project will create an opportunity for early imaging and therapy which can change the clinical course for patients. As a byproduct, this work will create a new clinical space in PCa by identifying men at risk for VM. The NanoVelcro vsnCTC Assay will provide a simple, minimally-invasive, and cost-effective means of identifying mCRPC patients at risk for VM, thereby allowing physicians to personalize patient monitoring, treatment, and therapy.