Glioblastoma – the most common and aggressive type of primary brain tumor – has complex genetic and signaling pathway defects. Therapies targeting a single defective protein or pathway have had limited efficacy.
A novel class of drugs that target BET proteins, which participate in “epigenetic” processes in the cell nucleus, has recently shown therapeutic potential against several blood cancers and a rare carcinoma. Jialiang Wang, Ph.D., assistant professor of Neurological Surgery, and colleagues assessed the effects of the BET inhibitor JQ1 on genetically heterogeneous glioblastoma samples. They demonstrate that JQ1 causes programmed cell death (apoptosis) of cultured glioblastoma cells with different genetic backgrounds, and that reducing the expression of individual BET proteins in the cells mimics JQ1’s effects. They also showed that JQ1 represses the growth of glioblastoma tumors in a mouse model.
The findings, reported in Clinical Cancer Research, suggest that epigenetic mechanisms – such as those mediated by BET proteins – may be commonly required by glioblastoma and that BET inhibitors like JQ1 may have broad utility for treating these genetically diverse tumors.
This research was supported in part by the American Brain Tumor Association and the Southeastern Brain Tumor Foundation.
