Targeting purinergic signalling in pancreatic cancer

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.