Evidence map›Paper›PMID 28930680›Full record

ArticleCell reports2017

Systematic Kinase Inhibitor Profiling Identifies CDK9 as a Synthetic Lethal Target in NUT Midline Carcinoma.

Johannes Brägelmann, Marcel A Dammert, Felix Dietlein, Johannes M Heuckmann, Axel Choidas, Stefanie Böhm, André Richters, Debjit Basu, Verena Tischler, Carina Lorenz and 24 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. [Research Progress on Pathogenesis and Treatment of NUT Carcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Report of the First International Symposium on NUT Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Article
  14. Nuclear protein of the testis midline carcinoma of the thorax.Japanese journal of clinical oncology · 2022
    Review
  15. Article
  16. Article
  17. Review
  18. Targeting transcription cycles in cancer.Nature reviews. Cancer · 2022
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors at 7 institutions in 3 countries.

Johannes BrägelmannMolecular Pathology, Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Department of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
Marcel A DammertMolecular Pathology, Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Department of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
Felix DietleinDepartment I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
Johannes M HeuckmannNEO New Oncology GmbH, Gottfried-Hagen-Str. 20, 51105 Cologne, Germany.
Axel ChoidasLead Discovery Center (LDC) GmbH, Otto-Hahn-Str. 15, 44227 Dortmund, Germany.
Stefanie BöhmMolecular Pathology, Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Department of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
André RichtersFaculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44221 Dortmund, Germany.
Debjit BasuFaculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44221 Dortmund, Germany.
Verena TischlerDepartment of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
Carina LorenzMolecular Pathology, Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Department of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
Peter HabenbergerLead Discovery Center (LDC) GmbH, Otto-Hahn-Str. 15, 44227 Dortmund, Germany.
Zhizhou FangFaculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44221 Dortmund, Germany.
Sandra Ortiz-CuaranDepartment of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
Frauke LeendersDepartment of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
Jan EickhoffLead Discovery Center (LDC) GmbH, Otto-Hahn-Str. 15, 44227 Dortmund, Germany.
Uwe KochLead Discovery Center (LDC) GmbH, Otto-Hahn-Str. 15, 44227 Dortmund, Germany.
Matthäus GetlikFaculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44221 Dortmund, Germany.
Martin TermatheFaculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44221 Dortmund, Germany.
Muhammad SallouhFaculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44221 Dortmund, Germany.
Zoltán GreffVichem Chemie Research Ltd., Herman Ottó u. 15, Budapest, Hungary.
Zoltán VargaVichem Chemie Research Ltd., Herman Ottó u. 15, Budapest, Hungary.
Hyatt Balke-WantDepartment of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany; Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
Christopher A FrenchDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Martin PeiferDepartment of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
H Christian ReinhardtDepartment I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
László ÖrfiVichem Chemie Research Ltd., Herman Ottó u. 15, Budapest, Hungary; Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes E. U.9, Budapest, Hungary.
György KériVichem Chemie Research Ltd., Herman Ottó u. 15, Budapest, Hungary.
Sascha AnsénDepartment I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
Lukas C HeukampDepartment of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany; Institute of Pathology, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
Reinhard BüttnerInstitute of Pathology, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
Daniel RauhFaculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44221 Dortmund, Germany.
Bert M KleblLead Discovery Center (LDC) GmbH, Otto-Hahn-Str. 15, 44227 Dortmund, Germany.
Roman K ThomasDepartment of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany; Institute of Pathology, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany; German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: roman.thomas@uni-koeln.de.
Martin L SosMolecular Pathology, Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Department of Translational Genomics, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany. Electronic address: martin.sos@uni-koeln.de.
University of Cologne · DETU Dortmund University · DELead Discovery Center (Germany) · DEUniversity Hospital Cologne · DEVichem Chemie (Hungary) · HUBrigham and Women's Hospital · USHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) and depend on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell-cycle arrest in these cells. Finally, RNA-seq and ChIP-based analyses reveal a BRD4-NUT-specific CDK9i-induced perturbation of transcriptional elongation. Thus, our data provide a mechanistic basis for the genotype-dependent vulnerability of NMC cells to CDK9i that may be of relevance for the development of targeted therapies for NMC patients.

Indexed as

Molecular Targeted TherapyBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorCyclin-Dependent Kinase 9Cyclin THEK293 CellsHigh-Throughput Screening AssaysHumansNeoplasmsNuclear ProteinsProtein Kinase InhibitorsRNA Polymerase IITranscription Elongation, GeneticTranscription FactorsTranscription, GeneticBRD4 protein, humanBromodomain Containing ProteinsCDK9 protein, humanCell Cycle ProteinsCyclin-Dependent Kinase 9Cyclin TNuclear ProteinsProtein Kinase InhibitorsRNA Polymerase IITranscription FactorsCDK9 inhibitorhigh-throughput screenNUT midline carcinomatranscriptional elongation

Identifiers

PMID28930680
PMCPMC5622049
OpenAlexW2756427490

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.