Pancreatic cancer is a serious disease of the pancreas with very poor prognosis and low survival rate (<8% of patients survive the disease). Furthermore, as oppose to other cancers where we have seen significant improvement of survival due to novel treatment developments, there has been hardly any improvement over the last decades for pancreatic cancer. A key aspect that leads to the progression of the disease is the so-called tissue (tumour) microenvironment (TME), which is essentially a cocktail of cells and biomolecules which interact with the tumour, making it resistant to treatment and helping it metastasise. Typically, therapies for pancreatic cancer are tested on animal models or on tumour cells cultured in 2D static conditions. While the complexity associated with animal studies improves the disease insight, they are expensive, complex, difficult to reproduce and many times unrepresentative. 2D single cell cultures are easy to use, reproducible and cost-efficient, however, they are unable to reproduce topologically, mechanically, biologically and biochemically the complex TME. More recently, 3D spheroid type ('tissue-spheres') cultures from human and mouse pancreatic cancer represent the state-of-the- art as they can be cultured for longer than 2D systems, they are suitable for drug screening. These can be established from small biopsy specimens, so in principle can be used to identify some tumour characteristics of individual patients. However, the self-organising nature of spheroids and the lack of mechanical and biochemical integrity limits the tuneability of the environment, therefore reducing the versatility of these models. An in vitro system with robust control of the biophysical, biochemical and biomechanical environment is currently lacking and would benefit the patients and the research community substantially as there is clear evidence in the state of the art that the biomechanical and biophysical environment can affect the disease progression, metastasis and response to treatment. The aim of our project is to develop a high fidelity pancreatic cancer model, which will enable patient & disease specific treatment optimization via robust control of various biochemical, biomechanical and biophysical features of the TME. More specifically, tailoring in a controlled manner parameters of the tumour microenvironment like extracellular matrix composition, stiffness (at levels that realistically occur in PDAC in vivo), interstitial flow rates (mimicking high or low vascularisation or avascular tumours), vessel sizes or fibrotic levels (mimicking dense or less dense fibrotic reaction) will enable the conduction of long term fundamental studies unravelling the interaction of each of those parameters with different cells of the tumour microenvironment. Underpinning such interactions at multiple levels, i.e., genetic, metabolic, will enable a better understanding of the evolution of the disease as well as the role of different TME configurations on driving signaling pathways for migration and metastasis. Furthermore, such a robust, tuneable, representative model for pancreatic cancer will help improve the success rate of emerging therapies and constitute a platform for personalised medicine.