Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
---|---|
Journal | Cancer Cell |
Volume | 26 |
Issue number | 6 |
Pages (from-to) | 909-922 |
Number of pages | 14 |
ISSN | 1535-6108 |
DOIs | |
Publication status | Published - Dec 2014 |
- Animals, Antineoplastic Agents, Cell Line, Tumor, Cyclin-Dependent Kinases, Enzyme Inhibitors, Gene Expression Regulation, Neoplastic, High-Throughput Screening Assays, Humans, Lung Neoplasms, Mice, Molecular Sequence Data, Neoplasms, Experimental, Sequence Analysis, DNA, Small Cell Lung Carcinoma, Transcription Factors, Transcription, Genetic, Xenograft Model Antitumor Assays
Research areas
ID: 135224591