The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer
Open accessAbstract
SUMMARY The MYC oncoproteins are thought to stimulate tumor cell growth and proliferation through amplification of gene transcription, a mechanism that has thwarted most efforts to inhibit MYC function as potential cancer therapy. Using a novel covalent inhibitor of cyclin-dependent kinase 7 (CDK7) to disrupt the transcription of amplified MYCN in neuroblastoma cells, we demonstrate downregulation of the oncoprotein with consequent massive suppression of MYCN-driven global transcriptional amplification. This response translated to significant tumor regression in a mouse model of high-risk neuroblastoma, without the introduction of systemic toxicity. The striking treatment selectivity of MYCN-overexpressing cells correlated with preferential downregulation of super-enhancer-associated genes, including MYCN and other known oncogenic drivers in neuroblastoma. These results indicate that CDK7 inhibition, by selectively targeting the mechanisms that promote global transcriptional amplification in tumor cells, may be useful therapy for cancers that are driven by MYC family oncoproteins.
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Cited by
Coactivator condensation at super-enhancers links phase separation and gene control
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MYC: Connecting selective transcriptional control to global RNA production
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Metadata
- Authors
- Chipumuro, E., Marco, E., Christensen, C. L., Kwiatkowski, N., Zhang, T., Hatheway, C. M., Abraham, B. J., Sharma, B., Yeung, C., Altabef, A., Perez-Atayde, A., Wong, K.-K., Yuan, G.-C., Gray, N. S., Young, R. A., & George, R. E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 159
- Issue
- 5
- Pages
- 1126-1139
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2170846478
- Cited by
- 631
- References
- 72
- FWCI
- 24.25
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer. https://app.cochat.ai/papers/10.1016/j.cell.2014.10.024
- The paper
- Chipumuro, E., Marco, E., Christensen, C. L., Kwiatkowski, N., Zhang, T., Hatheway, C. M., Abraham, B. J., Sharma, B., Yeung, C., Altabef, A., Perez-Atayde, A., Wong, K.-K., Yuan, G.-C., Gray, N. S., Young, R. A., & George, R. E. (2014). CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer. Cell. https://doi.org/10.1016/j.cell.2014.10.024
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