Conditional reprogramming in eyelid tumors: bridging the model gap in meibomian gland carcinoma

Abstract Eyelid tumors, particularly sebaceous carcinoma and meibomian gland carcinoma (MGC), are rare but highly aggressive malignancies characterized by diagnostic difficulty, early dissemination, and limited therapeutic options. Progress in understanding their biology and developing effective treatments has been hampered by the scarcity of robust, patient-derived preclinical models. Conditional reprogramming (CR) technology, which combines Rho-associated kinase (ROCK) inhibition with feeder fibroblast co-culture, enables rapid and reversible expansion of primary epithelial cells while preserving their genetic stability and lineage-specific phenotypic. Over the past decade, CR has emerged as a powerful platform for cancer modeling, drug sensitivity testing, and mechanistic studies across multiple epithelial malignancies. However, its application in ocular oncology remains underexplored. This review summarizes the biological principles and technical features of CR technology, highlights its established applications in epithelial cancer research, and focuses on its emerging relevance to eyelid tumors, particularly MGC. We further address current challenges, including tissue acquisition, standardization and reconstruction of the tumor microenvironment, and the future perspectives integrating CR with organoid culture, multi-omics profiling, and artificial intelligence-based analyses to advance functional precision oncology in eyelid malignancies.