Epithelial plasticity in lung cancer evolution: insights from organoids

Lung cancer remains the leading cause of cancer-related mortality and is often diagnosed at an advanced stage, limiting opportunities for early intervention. In vitro 3-dimensional lung organoid cultures recapitulate key features of human lung epithelial differentiation and are amenable to genetic manipulation. Epithelial plasticity during lung cancer evolution can be investigated by applying single-cell sequencing technologies to genetically engineered organoids, enabling the identification of mechanisms that suppress lung cancer initiation and progression. In this review, we consolidate recent findings and approaches in lung organoid–based cancer modeling and provide updated insights into lung cancer biology and future research directions.