Next-generation organoid models for colorectal cancer research
L. Francisco Lorenzo-Martín
École Polytechnique Fédérale de Lausanne (EPFL, Lausanne, Switzerland
Three-dimensional organoid culture technologies have revolutionized cancer research by allowing for more realistic and scalable reproductions of tumor structures. This has enabled better modelling of low-complexity cancer cell behaviors that occur over short periods of time. However, the currently available organoid systems lack the requisite multi-cellular diversity, tissue-level organization, biological durability, and experimental flexibility that are needed to capture complex oncological processes. Consequently, the study of many multifactorial cancer mechanisms is still not possible in vitro and instead requires the extensive use of animal models, which provide limited spatiotemporal resolution of cellular dynamics and come at a substantial ethical cost. To overcome these limitations, we have implemented tissue engineering and microfabrication technologies to develop topobiologically complex ex vivo cancer avatars. Focusing on colorectal cancer, we have generated miniature tissues consisting of long-lived gut-shaped colon epithelia (‘mini-colons’) that are able to undergo tumorigenesis in vitro and stably integrate cancer cells with their native tumor microenvironment. This system provides an unprecedented repertoire of experimental possibilities, which we illustrate through diverse applications. Altogether, these next-generation organoid models push the boundaries of ex vivo cancer research