Pancreatic ductal adenocarcinoma (PDAC) is an exceptionally aggressive cancer with a 5-year survival rate below 10%. It is resistant to traditional treatments and unresponsive to immunotherapy. New insights into the biology of PDAC are needed to identify novel therapeutic targets. Nerve invasion, defined as the presence of cancer cells along nerves and within different layers of nerve fibres, is a hallmark feature of PDAC. Patients that show signs of nerve invasion have a worse prognosis, higher risk of tumour recurrence, and suppressed anti-tumour immune responses. During PDAC, nerves form a dynamic microenvironment in which glial cells, neurons, stroma cells, cancer cells, and immune cells interact. The mechanistic basis of this communication and its effects on cancer progression remain undefined. Thus, in this project, cutting-edge transcriptomics technology preserving spatial information will be applied to human and murine PDAC tumour tissue sections. The cellular and molecular pathways dysregulated explicitly within cancer-invaded nerves will be identified, and the therapeutic potential of their targeting will be controlled in vitro and in vivo. The findings generated within this project could provide novel treatment strategies for PDAC and essential insights into the basic biology of cancer-nerve-immune interactions during tumorigenesis.
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