| Literature DB >> 25490451 |
Camilla L Christensen1, Nicholas Kwiatkowski2, Brian J Abraham2, Julian Carretero3, Fatima Al-Shahrour4, Tinghu Zhang5, Edmond Chipumuro6, Grit S Herter-Sprie1, Esra A Akbay1, Abigail Altabef1, Jianming Zhang5, Takeshi Shimamura7, Marzia Capelletti1, Jakob B Reibel1, Jillian D Cavanaugh1, Peng Gao1, Yan Liu1, Signe R Michaelsen8, Hans S Poulsen8, Amir R Aref1, David A Barbie1, James E Bradner1, Rani E George6, Nathanael S Gray5, Richard A Young9, Kwok-Kin Wong10.
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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 25490451 PMCID： PMC4261156 DOI： 10.1016/j.ccell.2014.10.019
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743