Life Sciences Faculties

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a five-year survival rate of ˜12.5% and is the fourth leading cause of cancer-related death in the western world, estimated to become the second leading cause of cancer related death by the year 2030. PDAC is characterized by a high metastatic burden leading to poor patient outcome. This capability to induce metastatic growth has been ascribed to specific sub-clones within tumours. Intra tumour heterogeneity in PDAC is also exemplified by the coexistence of a tumour hierarchy consisting of phenotypically different sub-populations that harbour unique proliferative, tumourigenic and chemoresistant capacities. Understanding PDAC hierarchies might be a crucial step to identify the cells of origin of PDAC, which will provide an important avenue that will allow deeper understanding of the disease and the development of more effective treatments for PDA patients. Given the ductal morphology of PDAC, ductal cells have for long been the main candidates as tumour initiating cells. However, more recent studies seemed to suggest that PDAC originate from non-ductal, endocrine or acinar cells, transdifferentiating into a ductal-like morphology. Recently, by utilizing commonly used genetic mouse model, we were able to identify a subpopulation of cells within the acinar cell population that is responsible for tumour initiation and serves as the cell of origin of PDAC in this mouse model. we have identified the gene signature of PDAC acinar cell of origin that consist of proliferation and stem cell associated gene signatures. This characterization might lead to the identification of early disease biomarkers and new therapeutic approaches to target the disease and improve the outcome PDAC patients.