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A bioengineered In vitro disease model of pancreatic ductal adenocarcinoma integrating cancer cell & fibroblast populations with a tuneable 3D tumour microenvironment to review metastatic progression.

Pancreatic cancer has been the most lethal of all cancers over the last 40 years and continues to be so today, despite significant improvements in it’s treatment. Current therapies do not prolong survival beyond 6 months on average, emphasising the need for the re-evaluation of current medicines in conjunction with the discovery of new therapies. Unfortunately, the current process of drug evaluation and discovery is also limited in that the laboratory bench models used to test drugs do not fully reflect the pancreatic tumour. In particular, these models do not account for the presence of other diseased cells around the cancer cells (known as “stellate cells”) and the dense and stiff organ tissue surrounding the cancer that they are embedded in (known as “desmoplasia”). Ultimately, poor representation in the lab increases the risk of failure in developing successful medicines, creating a bottleneck in the drug discovery process. This project seeks to address this issue by developing a laboratory model that incorporates these two characteristics of pancreatic cancer to create a more sophisticated representation of tumours in the laboratory setting. Using this model, we can understand how a combination of the cancer cells, the diseased stellate cells, and the dense desmoplasia all work together to resist current therapies, encourage cancer growth within the pancreas, and also to stimulate cancer spread to other sites. Through this understanding we can then uncover new ways of boosting current therapies in pancreatic cancer, develop new medicines, and ultimately, increase patient survival for this devastating condition.