Engineered cellular models to explore human disease heterogeneity

Ex vivo culture models provide powerful tools to interrogate the role of tumour heterogeneity in human cancers. Patient-derived organoids (PDOs) are emerging as powerful models to capture the genetic heterogeneity of human tumors. However, extrinsic factors present in the tumor microenvironment (TME) of a tumour, such as the presence of stromal cells and gradients of small molecules such as oxygen, also affect cancer phenotype and response to therapy. This talk will describe tissue-engineered platforms we have developed 1) to enable controlled assembly and disassembly of organoid structures to study the impact of both genetic and microenvironmental heterogeneity on tumor cell behavior and 2) to explore tumour microenvironment remodelling, heterogeneity in response to therapy, and potential to re-grow after therapy.