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

描述（申请人提供）：实体瘤是高度异质性的，包含许多不同的细胞类型，包括基质细胞。我们假设只有含有特殊异常信号通路的肿瘤细胞亚群将有助于治疗反应或

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.