Colon Organoids as Experimental Models to Study the Effect of Micro-Nanoparticles as a Driver of Early-Onset Colon Cancer.

Early-onset colorectal cancer (EOCRC) in people < 50 years of age has been rising globally, yet its causes remain unknown. Emerging evidence suggests that environmental factors, including exposure to micro-and nanoplastics (MNPs), may contribute to colorectal carcinogenesis. MNPs can enter the gastrointestinal tract through ingestion, translocate across the epithelial barrier via endocytosis or paracellular pathways, and interact directly with epithelial and immune cells. Once internalized, they may generate events associated with tumor initiation including oxidative stress, disruption of membrane integrity, pro-inflammatory signaling, and disruption of genomic and epigenomic stability. Patient-derived colorectal organoids offer a physiologically relevant and scalable 3D model that closely mimics the cellular architecture and genetic landscape of primary tumors. We highlight how organoid models can be leveraged to study the impact of MNPs on the key processes of inflammation, DNA damage, senescence, and epigenetic modifications. Furthermore, we discuss the application of organoid-based systems to model EOCRC driven by environmental exposures, including the integration of organoid platforms with high-throughput assays, omics profiling, and microfluidics to better capture MNP-induced pathogenic mechanisms. Altogether, colorectal organoids provide a powerful bridge between environmental plastic exposure and EOCRC etiology, offering a tractable platform to identify mechanistic pathways and potential biomarkers of early disease.