(PQB-4) Single cell analysis strategy for monitoring drug responses of tumors

描述（由申请人提供）：实体瘤是高度异质性的，含有许多不同的细胞类型，包括基质细胞。我们假设，只有含有特定异常信号传导途径的肿瘤细胞亚群才有助于治疗反应， 阻力我们建议使用新型多重单细胞“组学”来解锁对ADAPT疗法的完全反应的机制，ADAPT疗法是一种创新的组合疗法，旨在通过Wnt-PI 3 K-CDK轴靶向耐药（或休眠）晚期结直肠癌。在这项提案中，我们将采用全面的单细胞基因组学，转录组学和蛋白质组学研究在体外和体内肿瘤和基质细胞群的动态转变，之前和之后的标准5-FU化疗与ADAPT治疗直接在新鲜的结直肠癌活检样本。这项研究将使人们更深入地了解ADAPT治疗的反应和抗性途径，并开发出一种转化性单细胞技术（斯巴达），该技术可同时测量多种转录物和蛋白质，以监测和分层反应/抗性。

DESCRIPTION (provided by applicant): Solid tumors are highly heterogeneous and contain many distinct cell types including stromal cells. We hypothesize that only subsets of the tumor cells that harbor particular aberrant signaling pathways will contribute to therapeutic response or resistance. We propose using novel multiplex single cell "omics" to unlock the mechanisms of complete response to ADAPT therapy, an innovative combination therapy designed to target drug-resistant (or dormant) advanced colorectal cancer likely through Wnt-PI3K-CDK axis. In this proposal, we will employ comprehensive single cell genomics, transcriptomics, and proteomics to study in vitro and in vivo the dynamic transition of tumor and stromal cells populations, before and after standard 5-FU based chemotherapy versus ADAPT therapy directly in fresh colorectal cancer biopsies samples. This study will lead to greater insight into the pathways of response and resistance to ADAPT therapy and enable the development of a transformational single cell technology (SPARTA) that simultaneously measures multiple transcripts and proteins to monitor and stratify response/resistance.