Cyclin-dependent kinase 7 is a therapeutic target in high-grade glioma.
SA Greenall, YC Lim, CB Mitchell, KS Ensbey, BW Stringer, AL Wilding, GM O'Neill, KL McDonald, DJ Gough, BW Day, TG Johns
Oncogenesis | Published : 2017
High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the tumors unresponsive or able to adapt to therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient-derived primary HGG cell lines and ex vivo HGG patient tissue slices, using proliferation assays, microarray analysis, high-resolution respirometry,..View full abstract