Patient derived tumoroid to model rectal cancer under radiotherapy in a microphysiological system

Colorectal cancer is the third most prevalent cancer worldwide, with radiotherapy being a common treatment. Existing models of the gastrointestinal tract, including mouse and 2D immortalized human cell culture models, lack the combination of human representability and radiotoxicity. This study seeks to develop a human in vitro rectal cancer model representing radiotherapy treatment, using patient-derived tumor organoids to form monolayers. The anticipated cellular heterogeneity of organoid allows for a closer representation of the rectal physiology specificity and enables disease modeling. To give access to both the apical and basolateral sides and to enable integration into a mesofluidic microphysiological system (MPS) monolayers are seeded from the tumor organoid culture. This allows culturing in continuously perfused wells, recreating shear forces at play between the rectal tissue and the lumen. The monolayers are put under a radiotherapy set up, modelling fragmented irradiations.