Although advances in immunotherapy and targeted therapy have transformed the treatment landscape for many cancer patients, significant challenges still remain. For example, immune checkpoint inhibitors (ICI) are widely used for a number of cancers, but results have been disappointing with only ~40% response in patients with melanoma and <2% response in patients with pancreatic ductal carcinoma (PDAC). A notable difference between ICI ‘responders’ and ‘non-responders’ is the tumour microenvironment. This is particularly important in PDAC wherein the tumour is ‘impenetrable’ for attack by the immune system. With only 9% of PDAC patients surviving 5-years following diagnosis and the majority of melanoma patients still dying, improving anti-tumour immunity would undoubtedly save lives.
This proposal investigates how desmoglein-2 (DSG2), a cell surface adhesion molecule over-expressed by many cancer cells (including melanoma and PDAC), can be targeted to change the tumour microenvironment and inhibit cancer progression.