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

## TL;DR

This paper explores how micro-nanoparticles might contribute to early-onset colon cancer using organoid models to study their effects on cellular processes.

## Contribution

The paper introduces colorectal organoids as a novel experimental model to study the role of micro-nanoplastics in early-onset colon cancer.

## Key findings

- Colorectal organoids mimic tumor architecture and genetics, making them suitable for studying MNP effects.
- MNPs may induce tumor initiation through oxidative stress, inflammation, and genomic disruption.
- Organoid platforms can integrate with high-throughput assays and omics to study MNP-induced pathogenic mechanisms.

## Abstract

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.