Microphysiological systems to study colorectal cancer: state-of-the-art

Basic pre-clinical research based on 2D cultures have been very valuable in colorectal cancer (CRC) research but still have failed to improve patient prognostic outcomes. This is because they simply do not replicate what happens<i>in vivo, i.e.</i>2D cultured cells system cannot replicate the diffusion constraints usually found in the body. Importantly, they also do not mimic the dimensionality of the human body and of a CRC tumour (3D). Moreover, 2D cultures lack the cellular heterogeneity and the tumour microenvironment (TME) such as stromal components, blood vessels, fibroblasts, and cells of the immune system. Cells behave differently whether in 2D and 3D, in particular their different genetic and protein expression panels are very different and therefore we cannot fully rely on drug tests done in 2D. A growing field of research based on microphysiological systems involving organoids/spheroids or patient-derived tumour cells has become a solid base for a better understanding of the TME and as a result is a step towards personalized medicine. Furthermore, microfluidic approaches have also started to open possibilities of research, with tumour-on-chips and body-on-chips being used in order to decipher complex inter-organ signalling and the prevalence of metastasis, as well as CRC early-diagnosis through liquid biopsies. Herein, we focus on the state-of-the-art of CRC research with emphasis on 3D microfluidic<i>in vitro</i>cultures-organoids, spheroids-drug resistance, circulating tumour cells and microbiome-on-a-chip technology.