Grant: Operating Grant

With an overall 5-year survival rate under 5% and a median survival of 6 months, pancreatic cancer is the most devastating human malignancies. Moreover, the almost identical annual incidence and mortality rates make it the fourth leading cause of cancer-related death in Canada and worldwide. Despite enormous progress in medicine, the survival of patients with pancreatic cancer has not significantly improved over the last 40 years. The main reasons for the dismal prognosis of this type of cancer remains the late diagnosis of the disease, hence rendering surgical resection rates exceedingly low in addition to yielding poor clinical response to chemotherapy. This raises the urgent need for the identification of biomarkers to aid in the early detection of pancreatic cancer as well as in the development of new and effective treatment strategies. To attempt this goal, a better understanding of the detailed mechanisms of disease pathogenesis is critical. Previous studies have identified two signaling pathways aberrantly re-activated in cancerous pancreatic tissues compared to normal pancreatic tissues: the kRas and Notch pathways. Our results suggest that these two signaling pathways cooperate to promote pancreatic carcinogenesis. The general aim of our research is thus to understand how these two signaling pathways interact in order to promote progression of pancreatic cancer and evaluate whether inhibition of one of this pathway (the Notch pathway) blocks pancreatic cancer progression and thus can be envisaged as a new therapeutic avenue. To answer these questions, we will use both pancreatic cell lines and mouse models of pancreatic cancer.