Retinoblastoma: unveiling molecular pathogenesis and pioneering organoid-driven therapeutic innovations - PubMed
2 hours ago
- #Retinoblastoma
- #Precision medicine
- #Organoid model
- Retinoblastoma (RB) is the most common pediatric intraocular malignancy, driven by RB1 inactivation.
- Clinical challenges include treatment toxicity, relapse, and resistance.
- Traditional models fail to replicate human RB genetics or tumor heterogeneity, necessitating advanced in vitro platforms.
- Retinal organoids from human pluripotent or patient-specific stem cells enable 3D modeling of the tumor microenvironment, drug screening, and mechanistic studies.
- Key RB pathogenesis factors: RB1 loss, MYCN amplification, epigenetic dysregulation (e.g., METTL3-mediated m6A), and dysregulated pathways (PI3K/AKT/mTOR, Hedgehog).
- CRISPR-engineered organoids identify cone precursors as tumor origins and validate therapies like CDK4/6 inhibitors and sunitinib.
- Organoid limitations: high costs, variable success rates, incomplete immune/vascular mimicry, and limited scalability.
- Future directions: integrate multiomics, refine vascularization via 3D bioprinting, and develop immunocompetent models.
- Organoid technology has potential to advance personalized therapies and improve patient survival and quality of life.