Role of cingulin in FOLFIRINOX resistance

cingulin 在 FOLFIRINOX 耐药中的作用

• 批准号: 10816835
• 负责人: Jen Jen Yeh
• 金额: $ 1.51万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-16 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10816835
• 关键词: Genes; Modeling; Pancreatic Ductal Adenocarcinoma; Patient-Focused Outcomes; Patients; Phenotype; Resistance; Role; Sampling; Signal Transduction; Therapeutic; molecular subtypes; overexpression; parent grant; restoration; targeted treatment; treatment response; tumor; tumor microenvironment

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.

摘要 项目3的父母补助金旨在确定胰腺导管腺癌（PDAC）的作用 分子亚型和肿瘤微环境在患者样品的治疗反应中的作用。目标1 项目通过PurIST基于分子分型指导评估患者结局。项目目标3 决定针对肿瘤和间质的治疗。多样性补充项目扩大了 目标1和目标3中的若干次级目标。在正在研究的由PurIST定义的两种分子亚型中， 基底细胞样和经典型，基底细胞样亚型对一线治疗FOLFIRINOX耐药，主要 项目3中目标1、3的主题和理由。我们和其他人已经发现， 经典和基底样亚型，可能依赖于任一信号，但可塑性的调节剂 仍然不清楚。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 基底部肿瘤可能通过基因极性恢复对FOLFIRINOX产生反应， 扣带蛋白该项目将使用患者来源的模型，首先确定是否'切换'基底肿瘤的经典 通过改变CGN信号传导表型是可行的，其次，如果CGN过表达会恢复 肿瘤对FOLFIRINOX的基础敏感性。从长远来看，该项目的结果将决定是否切换 将基底肿瘤转移到经典肿瘤将促进靶向肿瘤和基质的额外治疗机会。