Journal article
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 | NATURE PUBLISHING GROUP | Published : 2017
Abstract
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,..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council of Australia (GNT1028552; TGJ). TGJ leads the Brain Cancer Discovery Collaborative, and all authors except DJG are members of the Brain Cancer Discovery Collaborative, which is supported by the Cure Brain Cancer Foundation. TGJ (GNT1117501) and DJG (GNT1063914) are supported by fellowships from the National Health and Medical Research Council of Australia and DJG is also supported by a grant from the US Department of Defense (CA150132). We are grateful to the Victorian Government's Operational and Infrastructure Support Program. We thank Dr D Dadley-Moore for editing the original manuscript.