Analysis of CTCs for Early Prediction of Response to Treatment in RCC

 描述（由申请人提供）：存在对肾细胞癌（RCC）的治疗反应的早期预测的显著需求，所述肾细胞癌（RCC）包括超过90%的肾癌。靶向治疗（TT）抑制血管生成可以是非常有效的，但疗效评价是有限的。治疗效果评价的标准治疗是在治疗12周后测量肿瘤大小。在等待12周的评估期间，高达20%的患者对治疗没有反应，忍受治疗的副作用以及肿瘤进展。我们的目标是在早期治疗阶段确定对治疗的反应。我们将进行一项前瞻性临床研究，将新的磁分离技术与新的纳米蛋白质组学技术相结合，以测量RCC治疗早期反应的生物学预测因子。如果成功，这项工作将从根本上改变目前癌症患者的治疗和监测模式。拟议的项目分为两个具体目标：目标1：开发磁筛技术，根据CAIX表面蛋白表达从RCC患者中分离CTC。目的2：分析RCC CTC和宿主免疫应答以预测对TT的应答。 该项目的效用包括：1）循环肿瘤细胞（CTC）和宿主免疫细胞的联合定量分析将允许加速预测TT两周内的临床反应。2)生物学反应的早期定量分析将减少不必要的毒性，并提供在发生显著进展之前转换为另一种活性药物的早期机会。我们的工作将允许医生通过测量对治疗的早期反应来个性化地定制靶向治疗的用途。此外，磁筛技术正在开发中，用于富集其他实体瘤中的循环肿瘤细胞（CTC），以进行个性化癌症治疗。因此，拟议的技术和临床研究代表了标准护理的实质性进步，并在循环肿瘤细胞，个性化医疗，癌症生物学和转化分子诊断等多个领域具有巨大的变革潜力。

 DESCRIPTION (provided by applicant): A significant need exists for early prediction of therapeutic response in Renal Cell Carcinoma (RCC), which comprises over 90% of kidney cancer. Targeted therapies (TT) inhibiting angiogenesis can be highly effective, yet evaluation of therapy efficacy is limited. The standard of care in evaluation of therapeutic efficacy is to measure tumor size after 12 weeks of therapy. While awaiting their 12 week evaluation, up to 20% of patients do not respond to therapy, enduring side effects of the therapies together with tumor progression. We aim to identify response to therapy in the early treatment phase. We will perform a prospective clinical study that combines novel magnetic separation techniques with new nanoproteomic technology to measure biological predictors of early response to therapy in RCC. If successful, this work would radically shift the current treatment and monitoring paradigm of cancer patients. The proposed project is organized into two specific aims: Aim 1: Develop magnetic sifter technology to isolate CTCs from patients with RCC, based on CAIX surface protein expression. Aim 2: Profile RCC CTCs and host immune response to predict response to TT. The utility of the project includes: 1) Combined quantitative analysis of circulating tumor cells (CTCs) and host immune cells will allow accelerated prediction of clinical response within two weeks of TT. 2) Early quantitative analysis of biologic response will reduce unnecessary toxicity as well as provide an early opportunity to switch to another active agent before significant progression occurs. Our work will allow physicians to individually tailor the us of targeted therapeutics by measuring early response to treatment. Additionally, the magnetic sifter technology is being developed for enriching circulating tumor cells (CTC) in other solid tumors for personalized cancer therapy. Therefore, the proposed technology and clinical studies represent a substantial advance over the standard care and has great transformative potential in multiple areas of circulating tumor cells, personalized medicine, cancer biology, and translational molecular diagnostics.