RESUMEN
Three-dimensional (3D) in vitro models are essential in cancer research, but they often neglect physical forces. In our study, we combined patient-derived tumor organoids with a microfluidic organ-on-chip system to investigate colorectal cancer (CRC) invasion in the tumor microenvironment (TME). This allowed us to create patient-specific tumor models and assess the impact of physical forces on cancer biology. Our findings showed that the organoid-on-chip models more closely resembled patient tumors at the transcriptional level, surpassing organoids alone. Using 'omics' methods and live-cell imaging, we observed heightened responsiveness of KRAS mutant tumors to TME mechanical forces. These tumors also utilized the γ-aminobutyric acid (GABA) neurotransmitter as an energy source, increasing their invasiveness. This bioengineered model holds promise for advancing our understanding of cancer progression and improving CRC treatments.
RESUMEN
Recreating 'living organs' with groundbreaking organ-on-a-chip (OOC) technologies is facilitating a new era of drug discovery. Studies by Huh et al. and Ronaldson-Bouchard et al. underscore advances made over a decade, spanning single organ functionality to interconnected organs, that enable examination of drug toxicities and disease pathogenesis in reconstituted tissues.