Abstract:
Glioblastoma (GBM), the most aggressive primary brain tumor, is marked by high recurrence rates and poor survival outcomes. Current therapies have limited efficacy due to the tumor's ability to evade treatment by leveraging diverse molecular mechanisms. This study explores the impact of combined treatment with Belinostat, a histone deacetylase (HDAC) inhibitor, and AsiDNA, a DNA repair inhibitor, on gene expression in GBM. Utilizing data from the U-87 GBM cell line, differential gene expression analysis identified 1174 uniquely affected genes when both treatments were used, compared to either treatment alone. Significant suppression of critical genes, such as SRSF2, which drives tumor survival through alternative splicing, was observed. The combination therapy disrupted key pathways like DNA damage response and TP53-mediated transcription, enhancing DNA damage susceptibility and reducing tumor cell survival. These findings suggest that integrating Belinostat and AsiDNA offers a promising approach to overcome resistance developing biomarkers to personalize therapy.
