Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor
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Young_Targeting transcriptional.pdf
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Author(s)
Christensen, Camilla L.
Carretero, Julian
Al-Shahrour, Fatima
Zhang, Tinghu
Chipumuro, Edmond
Herter-Sprie, Grit S.
Akbay, Esra A.
Altabef, Abigail
Zhang, Jianming
Shimamura, Takeshi
Date Issued
December 2014
Journal
Cancer Cell
Publisher
Elsevier
Citation
Christensen, Camilla L. et al. “Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor.” Cancer Cell 26, no. 6 (December 2014): 909–922. © 2014 Elsevier Inc
Version
Author's final manuscript
Abstract
Small cell lung cancer (SCLC) is an aggressive disease with high mortality, and the identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library, we observe that SCLC is sensitive to transcription-targeting drugs, in particular to THZ1, a recently identified covalent inhibitor of cyclin-dependent kinase 7. We find that expression of super-enhancer-associated transcription factor genes, including MYC family proto-oncogenes and neuroendocrine lineage-specific factors, is highly vulnerability to THZ1 treatment. We propose that downregulation of these transcription factors contributes, in part, to SCLC sensitivity to transcriptional inhibitors and that THZ1 represents a prototype drug for tailored SCLC therapy.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.ccell.2014.10.019
