Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Tidsskrift | Cancer Cell |
Vol/bind | 26 |
Udgave nummer | 6 |
Sider (fra-til) | 909-922 |
Antal sider | 14 |
ISSN | 1535-6108 |
DOI | |
Status | Udgivet - dec. 2014 |
ID: 135224591