Pancreatic cancer is a devastating disease with a very poor prognosis. Pancreatic ductal adenocarcinoma (PDAC) is characterised by excessive deposition of extracellular matrix proteins which ultimately leads to a stroma with increased stiffness. High stiffness gives rise to perpetuation of the disease through activation of stromal components that further exacerbate disease aetiology. This process is termed as mechanosensing where the cell is able to mechanically sense the external environment resulting in mechanotransduction, which is the conversion of these mechanical cues into biochemical ones leading to intracellular changes that allow cells to adapt to their microenvironment. Studies presented here, focused on pancreatic stellate cells (PSCs), fundamental stromal cells that play a critical role in the maintenance of the pancreatic stroma and upholding of tissue homeostasis. In diseased states, PSCs can negatively affect tissue regulation and aid in a positive feedback mechanism to intensify disease pathology. Through rigidity guided migration i.e. durotaxis, cells mechanically sense their substrate and generate forces to migrate to more rigid regions. Here, the fabrication of substrates that mimic the stiffness of healthy and fibrotic tissue which would be seen in vivo in pancreatic cancer, the effect that these substrates have on focal adhesion dynamics and subsequent cell migration is demonstrated.

Another major hurdle faced in pancreatic cancer is resistance acquired in response to drug therapy. This resistance can occur in the form of a physical barrier like the fibrotic stroma that hampers effective drug delivery, or drug resistance in response to upregulation of various signalling pathways leading to drug efflux and increased drug metabolism. Gemcitabine is currently the standard chemotherapeutic used to treat pancreatic cancer but many patients acquire resistance to therapy within the first few weeks of treatment. Here, it is shown that using combination therapy gemcitabine and G protein coupled estrogen receptor (GPER) agonist G1, increased cell apoptosis and decreased cell proliferation demonstrating that combination therapy could offer a possible therapeutic route in targeting this disease.