Project 50.1: Targeting pancreatic cancer invasion with novel therapeutics

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Pancreatic cancer (PC) survival is devastatingly low with few patients surviving more than 5 years postdiagnosis due to the prevalence of metastatic disease. Currently treatment options have limitedefficacy with no drugs specifically targeting the pathways implicated in metastasis and thus noveltherapeutic approaches are urgently required. We have recently completed a 3D spheroid screen, inthe presence of stromal cells, of clinically approved drugs to identify those that can be repurposed toblock PC invasion. We now need to validate these hits and elucidate the molecular mechanism thatunderpins suppression of invasion.One of our top hits was an anti-fibrinolytic, an exciting and novel discovery. Our preliminary datasuggests impacts on both cancer and stromal cells; we now need to untangle the molecular pathways.We also want to test if this inhibitor blocks invadopodia activity in PC cells. Invadopodia are specialisedcancer cell structures that facilitate invasion. This project aims to bring together our screen discoverieswith our existing expertise in invadopodia biology to develop novel therapeutics to target pancreaticcancer invasion.