Deciphering the impact of genetic and microenvironmental variation on pancreatic ductal adenocarcinoma (PDAC) cell phenotype and response to therapy

Survival rates for many cancer types, in particular pancreatic cancer, are poor and there is a need for new therapies to be developed. Developing effective cancer therapies is difficult because cells in different locations within a tumour do not respond equally well to treatment. This is because tumour cell properties are influenced by their genetic profiles and the environmental conditions they experience. Tumours are complex environments containing multiple cell types and variable chemical conditions that affect each cell's response to therapy. In particular, immune cells in the tumour environment strongly influence tumour cell properties and how well the tumour cells respond to therapies. A better understanding of how tumour cells with different genetic properties and immune cells interact and talk to each other in different locations within tumours could provide a basis for developing new drugs that modify these interactions to make current tumour-killing therapies more effective. Understanding these interactions is challenging in animal models however. Here we propose to use tissue engineered culture models to characterize the molecular interactions between immune and tumour cells in different tumour environments to identify interactions that can be modified to improve pancreatic tumour cell response to therapy.