Cancer Biology Commons^™

Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma, Enyuan Shang, Trang T. T. Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM.We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199. Combined treatment with BH3-mimetics and THZ1 led to synergistic growth reduction in GBM models. Reduction in cellular viability was accompanied by significant cell death induction …