期刊
CANCER CELL
卷 26, 期 6, 页码 909-922出版社
CELL PRESS
DOI: 10.1016/j.ccell.2014.10.019
关键词
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资金
- Danish Cancer Society [R56-A3106-12-S2]
- Deutsche Forschungsgemeinschaft [HE6897/1-1]
- National Institutes of Health [CA122794, CA140594, CA163896, CA166480, CA154303, CA120964, R01 CA179483-01A1]
- Thoracic Foundation
- Susan Spooner Foundation
- MIT-DFCI Bridge grant
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.
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