Most high-throughput target discovery screens for glioblastoma have been limited to in vitro models with uncertain physiological relevance. Here, Jeremy Rich and colleagues perform two parallel RNA interference screens for transcriptional regulators, comparing an in vitro screen in cell lines to an in vivo screen that recapitulates the tumour microenvironment. They find several transcriptional elongation factors that are specifically required for glioblastoma cell survival in vivo, particularly the transcriptional pause release factor JMJD6 which is highly expressed in gliomas. This type of in vivo functional screen has the potential to uncover novel therapeutic targets for cancer that have not been identified in previous in vitro approaches.
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