Role of cingulin in FOLFIRINOX resistance

摘要 父母赠款的项目3试图确定胰腺导管腺癌(PDAC)的作用。 患者样本治疗反应中的分子亚型和肿瘤微环境。目标1 PROJECT通过PURIST根据分子亚型指导评估患者的结果。该项目的目标3 确定针对肿瘤和间质的治疗方法。多样性补充项目扩大了以下成果 目标1和目标3内的几个子目标。在由Purist定义的正在研究的两个分子亚型中， 基底样和经典型，基底样亚型对一线治疗FOLFIRINOX，主要是 项目3中目标1、3的主题和原理。我们和其他人发现，在 经典的和基底样的亚型，可能依赖于任何一个信号，但可塑性的调节者 目前仍不清楚。与项目3目标1相关，多样性补充项目将确定患者是否患有 通过基因的极性恢复，基底肿瘤可能对FOLFIRINOX产生反应 银杏林。该项目将首先使用患者衍生的模型来确定是否将基础肿瘤‘切换’为经典肿瘤 通过改变CGN信号的表型是可行的，第二，如果CGN过表达会恢复 基础肿瘤对FOLFIRINOX的敏感性。从长远来看，这个项目的结果将决定是否要转换 基底性肿瘤向经典性肿瘤的转变将促进针对肿瘤和间质的额外治疗机会。

Abstract Project 3 of the parent grant seeks to determine the role of pancreatic ductal adenocarcinoma (PDAC) molecular subtype and the tumor microenvironment in treatment response in patient sample. Aim 1 of the project evaluates patient outcome based on molecular subtyping guidance through PurIST. Aim 3 of the project determines therapies that target the tumor and stroma. The diversity supplement project expands on results of several sub-aims within Aims 1 and 3. Of the two molecular subtypes defined by PurIST that are being studied, basal-like and classical, the basal-like subtype is resistant to the first-line therapy FOLFIRINOX, the main theme and rationale for Aims 1, 3 in Project 3. We and others have found that there may be plasticity between the classical and basal-like subtype that may be dependent on either signaling, but the regulators of plasticity remain unclear. Relevant to Project 3 Aim 1, the diversity supplement project will determine if patients with basal tumors may become responsive to FOLFIRINOX through restoration of polarity through the gene cingulin. This project will use patient-derived models to first determine if ‘switching’ a basal tumor to a classical phenotype is feasible through alteration of CGN signaling, and second, if CGN overexpression will restore basal tumor sensitivity to FOLFIRINOX. In the long run, results from this project will determine if switching basal tumors to classical will facilitate additional therapeutic opportunities that target the tumor and stroma.