Pancreatic Cancer (PC) is one of the deadliest forms of cancer. Thus, there is an urgent need to find new therapeutic strategies and valid pharmacological targets to improve the grim survival prospect that face PC patients. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC). Despite increased knowledge about the biology of PC, the mortality to incidence ratio remains high and has barely changed over the last few decades. Long-term survival rates remain very low, with only about 9% of diagnosed patients surviving for 5 years and 20% of patients living one year post-diagnosis. The average life expectancy after PC diagnosis is just 6 months, as PC is usually diagnosed at the late, metastatic stage when the tumour is not susceptible to current standard of care treatment. Moreover, PDAC exhibits high chemo-and radiotherapy resistance. One cause of this resistance is the huge heterogeneity and plasticity of PDAC tissues. In addition, PDAC has a characteristic diffuse stroma called desmoplasia. This mixture of fibroblasts, blood vessels and immune cells forms a dense environment which, by expressing multiple molecules (e.g. chemokines, EGFs, Cox-2), interacts with cancer cells and influences tumour progression and invasion.

Our group aims to identify the cell signalling pathways crucial for pancreatic cancer progression in order to develop novel therapeutic strategies. We recently demonstrated the importance of the ABC transporter ABCC3 in PDAC progression and identified it as a potential therapeutic agent. We further established that ABCC3 releases the bioactive lipid lysophoshatidyinositol (LPI) that activates its receptor G protein coupled receptor 55 (GPR55) that we found to play a crucial role in PDAC. We also demonstrated that pharmacological inhibition of ABCC3 using its specific inhibitor MIC-715 greatly pancreatic cancer growth.

This work was supported by Pancreatic Cancer
Research Fund and Avner Pancreatic Cancer Foundation