Molecular etiology and therapeutic advances in retinoblastoma.
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Retinoblastoma is an aggressive intraocular tumor that originates from the developing retina in early childhood. Biallelic loss of RB1 has long been considered the main event for initiating RB development in most cases. Additional genetic events following RB1 loss, such as MYCN amplification, were found to be required for RB progression. Advancements in next-generation sequencing technologies have enabled a deeper understanding of the contributors to RB origin and development, revealing that secondary genetic alterations following RB1 inactivation are infrequent. In contrast, epigenetic changes were shown to be critical promoters of RB tumorigenesis. Several epigenetic regulators, including DNA methylation, histone modifications and noncoding RNAs, have been proven to be dysregulated in RB, contributing to its progression. Understanding the underlying mechanisms involved in RB and exploring new treatment strategies is a crucial step toward developing more effective and less invasive therapeutic approaches that can improve patient outcomes. This review summarizes the significant genetic and epigenetic alterations involved in RB tumorigenesis, current therapeutic strategies, and future treatment prospects for patients with RB.