S2627
Radiobiology - Translational radiobiology
ESTRO 2026
fractionated RT or control conditions. Differential sgRNA enrichment was used to prioritize candidates, followed by secondary validation assays and network- based functional annotation. Both established glioma cell lines and patient-derived primary cultures were incorporated to capture clinical and molecular
diversity. Results:
Integrated analysis of EPIKOL, DDRKOL, and druggable-genome screening data revealed
convergent radiosensitizing vulnerabilities within DNA repair, chromatin remodeling, and RNA-processing pathways. Distinct signatures emerged between classical and IDH-mutant glioma models, underscoring genotype-specific RT modulators. Validation studies confirmed several novel chromatin regulators and transcriptional cofactors whose loss significantly enhances RT-induced cytotoxicity. These findings demonstrate that combinatorial CRISPR screening is a powerful strategy to dissect mechanistic heterogeneity in RT response. Conclusion: Focused CRISPR library screens integrating epigenetic, DNA-damage, and druggable targets provide a robust framework for discovering regulators of RT response in glioma. Our results uncover candidate genes and pathways that may serve as biomarkers or therapeutic targets to overcome radioresistance, supporting the development of more effective RT-based treatment strategies for glioma patients. Keywords: CRISPR screens, glioma, novel radiosensitizer
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