3D gastrointestinal models and organoids to study metabolism in human colon cancer.

Recent advances in the field of cancer metabolism raised awareness for the importance of the tumour microenvironment in tumour growth and progression. The initial theory by Heinrich Warburg was that cancer cells had a deficient oxidative respiration and thus had to perform aerobic glycolysis to produce energy. However, further research suggested that there is a metabolic reprogramming within the tumour microenvironment, controlled by communication between tumour and stromal cells. The importance of this communication exposes the need to use complex models in cancer research. Until recently, classic cell models included immortalized 2D cell lines or patient-derived tumour xenografts. Despite having contributed to many discoveries, these models present many limitations. Improved models are now being developed using 3D cell culture technology. These models are more physiologically relevant allowing the co-culture of different cells types and establishing a gradient concentration of solutes. Recent developments in organoid technology contributed largely to the expansion of 3D cell technology. Organoids can be developed from different tissues including tumours, representing the cell population and spatial organization of the tissue of origin. In the field of cancer metabolism, the interaction of different cell types, the stroma, and the different solutes and oxygen concentrations are crucial parameters. Current models to study metabolism either include only one cell population or are unable to represent solute/oxygen gradients or to collect samples in a proficient manner. The characteristics of organoid culture thus makes them a potent model to use in metabolic studies, drug development, disease model or even personalized medicine.