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Targeting purinergic signalling in pancreatic cancer

靶向胰腺癌中的嘌呤信号

基本信息

批准号：
2396417
负责人：
金额：
--
依托单位：
Queen Mary University of London
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2396417
关键词：
Targeting purinergic signalling pancreatic cancer

项目摘要

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that shows limited response to new and conventional anti-cancer treatments, largely as a result of its characteristic dense fibrosis. There is a need to understand the cancer-protective mechanisms of fibrosis to discover possible therapeutic targets. One pathway known to be cytoprotective in highly hypoxic environments is purinergic signalling, but little is known about its importance in pancreatic cancer. This pathway is highly druggable and affects relevant biological processes, including immune cell behaviour, cell proliferation and glycolysis. The aim of this project is to interrogate the potential role of purinergic signalling in PDAC. As a starting point, the expression of key purinergic signalling genes in PDAC patients has been analysed using public databases. In preliminary bioinformatic analysis, gene expression has been correlated to clinical data to identify possible targets, with the receptor P2Y2 showing a correlation with clinical outcome and a link with cell-adhesion and immune related genes. The significance of this receptor, and other potential purinergic targets will be studied using overexpression, silencing and drug-based approaches using a 3D multicellular spheroid model of PDAC, with the aim of determining potential novel therapeutic targets.

胰腺导管腺癌(PDAC)是一种致命性疾病，对新的和传统的抗癌治疗反应有限，主要是由于其特有的致密纤维化。有必要了解纤维化的癌症保护机制，以发现可能的治疗靶点。已知的在高度低氧环境中具有细胞保护作用的一个途径是嘌呤能信号，但人们对其在胰腺癌中的重要性知之甚少。这种途径具有很强的可药性，并影响相关的生物学过程，包括免疫细胞行为、细胞增殖和糖酵解。这个项目的目的是询问嘌呤能信号在PDAC中的潜在作用。作为一个起点，利用公共数据库分析了PDAC患者中关键的嘌呤能信号基因的表达。在初步的生物信息学分析中，基因表达与临床数据相关，以确定可能的靶点，其中受体P2Y2显示与临床结果相关，并与细胞黏附和免疫相关基因有关。该受体和其他潜在的嘌呤能靶点的意义将通过使用PDAC的3D多细胞椭球模型，通过过度表达、沉默和基于药物的方法来研究，目的是确定潜在的新治疗靶点。