Development of in vitro models of common cancers of the urological system to investigate the effects on the tumour microenvironment

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The cellular microenvironment (which includes matrix rigidity, soluble factors, cell-cell and cell-extracellular matrix (ECM) interactions) is instrumental to the response of cancer cells to treatment. Low oxygen tension (hypoxia) within the tumour and surrounding tissues greatly reduces the effectiveness of radiotherapy for prostate and bladder cancer patients.Cancer cells cultured in 3D can recapitulate the in vivo tumours to a significantly higher degree when compared to monolayer cultures. The proliferation of tumour cells cultured in 3D is typically slower and hence more physiologically relevant than that of monolayer cultures. In this project 3D tumour models will be developed that better recapitulate the tumour microenvironment and improve the in vitro assessment of cancer therapeutics modalities.We have established fibrous scaffolds and 3D cancer models using synthetic (self-assembling peptides) and natural (alginate, collagen) hydrogels that better mimic the fibrous component of tumours. Here, we aim to develop 3D models with tumour cells seeded within the biomaterials to bridge the gap between flat 2D in vitro culture and in vivo experiments. These will be cultured in a perfusion bioreactor with modifiable oxygen delivery or in the presence of hypoxia inducers to mimic the hypoxic environment seen in solid tumours to allow us to assess the role of hypoxia in treatment resistance, and more specifically in radiation response.