Combined HDAC and Bromodomain Protein Inhibition Reprograms Tumor Cell Metabolism and Elicits Synthetic Lethality in Glioblastoma.

ABSTRACT: Purpose: Glioblastoma remains a challenge in oncology, in part due to tumor heterogeneity.Experimental Design: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems.Results: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that the combination of histone deacetylase (HDAC) inhibition and bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells. Transcriptome-based GSEA analysis suggests that metabolic reprogramming is involved with synergistic reduction of oxidative and glycolytic pathways in the combination treatment. Extracellular flux analysi

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6095717 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature