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Anticancer agents

CDK7 inhibition suppresses MYC-dependent cancer

Nature Reviews Drug Discovery volume 14, page 16 (2015)Cite this article

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Many human cancers depend on deregulated expression of MYC family members for growth and proliferation. Deregulated MYC is transcriptionally regulated by 'super-enhancers' (clusters of enhancers that are occupied densely by transcription factors, cofactors and chromatin regulators). Here, the authors report that a covalent inhibitor of cyclin dependent kinase 7 (CDK7), THZ1, disrupts the transcription of amplified MYCN in neuroblastoma cells and induces tumour regression in a mouse model of neuroblastoma. The selectivity of THZ1 for MYCN-amplified cells correlates with reduced expression of super-enhancer-associated oncogenic drivers, including MYCN.

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References

  1. Chipumuro, E. et al. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell 159, 1126–1139 (2014)

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  1. Sarah Crunkhorn
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Crunkhorn, S. CDK7 inhibition suppresses MYC-dependent cancer. Nat Rev Drug Discov 14, 16 (2015). https://doi.org/10.1038/nrd4513

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