ABS 085: The Effects of Belinostat and Long-Term AsiDNA Treatment on Gene Expression in Glioblastoma

Tehreem Fatima

Van Wickle (2025) Volume 1, ABS 085

Introduction: Glioblastoma (GBM), the most aggressive form of primary brain tumor, is characterized by a dismal prognosis due to high recurrence rates and resistance to existing treatments. Current therapies, including surgical resection, radiation, and chemotherapy, have limited efficacy because GBM leverages diverse molecular mechanisms to evade therapeutic intervention. This study investigates the synergistic effects of Belinostat, a histone deacetylase (HDAC) inhibitor, and AsiDNA, a DNA repair inhibitor, on GBM gene expression to address these challenges. Using the U-87 GBM cell line, differential gene expression analysis identified 1174 genes uniquely altered when both drugs were used in combination compared to monotherapy.

Among the affected genes, SRSF2, a key regulator of alternative splicing that supports tumor survival, was significantly suppressed. Furthermore, pathway analysis revealed disruptions in critical cellular processes, including DNA damage response and TP53-mediated transcription. The combination therapy effectively increased DNA damage susceptibility, impairing the tumor's ability to repair itself, and enhanced apoptosis, reducing overall tumor cell survival.

These findings suggest that combining Belinostat and AsiDNA may overcome therapeutic resistance by targeting multiple pathways simultaneously. This approach holds potential for developing more effective treatments. In the future, this study hopes to identify biomarkers to personalize therapy, advance GBM management, and improve patient outcomes.