AI Article Synopsis
- Triple-negative breast cancer (TNBC) is highly aggressive and shows complex genetics but uniform gene expression.
- Researchers believe that TNBC relies heavily on continuous transcription of certain critical genes and is sensitive to transcription inhibitors.
- The study found that TNBC cells depend on the CDK7 enzyme, and inhibiting it leads to cell death, suggesting that targeting CDK7 could be an effective treatment for TNBC.
Article Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that TNBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing kinase inhibitors and CRISPR/Cas9-mediated gene editing, we show here that triple-negative but not hormone receptor-positive breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. TNBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An "Achilles cluster" of TNBC-specific genes is especially sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in TNBC and CDK7 inhibition may be a useful therapy for this challenging cancer.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583659 | PMC |
| http://dx.doi.org/10.1016/j.cell.2015.08.063 | DOI Listing |
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