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.

抽象的 母基金项目 3 旨在确定胰腺导管腺癌 (PDAC) 的作用 患者样本中治疗反应的分子亚型和肿瘤微环境。 项目通过 PurIST 的目标 3 根据分子分型指导评估患者结果。 确定针对肿瘤和基质的疗法。多样性补充项目扩展了研究结果。 目标 1 和 3 中的几个子目标。在正在研究的 PurIST 定义的两种分子亚型中， basal-like和classical，basal-like亚型对一线治疗FOLFIRINOX有耐药性，FOLFIRINOX是主要的治疗药物 项目 3 中目标 1、3 的主题和基本原理。我们和其他人发现，项目 3 中的目标 1、3 之间可能存在可塑性 经典亚型和类基底亚型可能依赖于任一信号传导，但可塑性调节因子 与项目 3 目标 1 相关的问题仍不清楚，多样性补充项目将确定患者是否患有以下疾病： 基底肿瘤可能通过基因恢复极性而对 FOLFIRINOX 产生反应 该项目将使用源自患者的模型来首先确定是否将基底肿瘤“转换”为经典肿瘤。 通过改变 CGN 信号传导，表型是可行的，其次，CGN 过度表达是否会恢复 从长远来看，该项目的基础结果将决定是否转换。 基底肿瘤到经典肿瘤将促进针对肿瘤和间质的额外治疗机会。