Unraveling the genetic landscape of high-risk retinoblastoma through transcriptome profiling

Retinoblastoma (RB), a rare and aggressive pediatric cancer, presents severe challenges in treatment due to its genetic complexity. It's crucial to develop tailored therapies for high-risk RB cases. We conducted transcriptome profiling to investigate gene expression patterns and identify genetic factors associated with high-risk RB. Molecular modeling-based drug discovery was subsequently used to identify novel compounds targeting high-risk retinoblastoma genetic factors. In our research, we identified dysregulated genes, prioritizing polo-like kinase 1 (PLK1) for drug targeting. Further investigation of the PLK1 gene revealed its relationships with microRNAs (miRNAs), transcription factors (TFs), and protein kinases, implying its role in RB. Differentially expressed PLK1 correlates with dysregulated cell cycle, suggesting its involvement in RB progression. Molecular docking, simulations, and thermodynamic free energy calculations assessed the potential of small drug-like molecules, leading to the identification of two potent PLK1 inhibitors, compounds 1950 and 2760. These inhibitors hold promise for inhibiting the growth of RB cells. Our findings underscore PLK1 as a promising therapeutic target, highlighting computational approaches' efficacy in RB research.