Evidence map›Paper›PMID 41505030›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2026

Disrupting CDK9 activity suppresses triple-negative breast cancer and is enhanced by EGFR Inhibition.

Vera E van der Noord, Ronan P McLaughlin, Jessica S Karuntu, Jichao He, A Mieke Timmermans, Sunita K C Basnet, Yi Long, Sarah Al Haj Diab, Solomon Tadesse, Natalie Proost and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Review
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

19 authors.

Vera E van der Noord *Division of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, 2300 RA, The Netherlands. v.e.van.der.noord@lacdr.leidenuniv.nl.ORCID http://orcid.org/0000-0002-9894-3239
Ronan P McLaughlin *Division of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, 2300 RA, The Netherlands.
Jessica S KaruntuDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, 2300 RA, The Netherlands.
Jichao HeDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, 2300 RA, The Netherlands.
A Mieke TimmermansDepartment of Medical Oncology, Erasmus MC Cancer Institute, Cancer Genomic Netherlands, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands.
Sunita K C BasnetDrug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
Yi LongDrug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
Sarah Al Haj DiabDrug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
Solomon TadesseDrug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
Natalie ProostPreclinical Intervention Unit, Netherlands Cancer Institute, Mouse Clinic for Cancer and Aging (MCCA), Amsterdam, 1066 CX, The Netherlands.
Bastiaan van GerwenPreclinical Intervention Unit, Netherlands Cancer Institute, Mouse Clinic for Cancer and Aging (MCCA), Amsterdam, 1066 CX, The Netherlands.
Bjørn SiteurPreclinical Intervention Unit, Netherlands Cancer Institute, Mouse Clinic for Cancer and Aging (MCCA), Amsterdam, 1066 CX, The Netherlands.
Marieke van de VenPreclinical Intervention Unit, Netherlands Cancer Institute, Mouse Clinic for Cancer and Aging (MCCA), Amsterdam, 1066 CX, The Netherlands.
Chantal PontDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, 2300 RA, The Netherlands.
Sylvia E Le DévédecDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, 2300 RA, The Netherlands.
John W M MartensDepartment of Medical Oncology, Erasmus MC Cancer Institute, Cancer Genomic Netherlands, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands.
Shudong WangDrug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
Yinghui ZhangDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, 2300 RA, The Netherlands.
Bob van de WaterDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, 2300 RA, The Netherlands. b.water@lacdr.leidenuniv.nl.

Funding

Dutch Cancer Society 2021-14546European Research Council 322737European Research Council 767854
6 · The paper itself

Abstract

purposeCDK9, in complex with cyclin T1 or T2, is essential for mRNA transcription by enabling paused RNA polymerase II to proceed into elongation. Increasing evidence highlights CDK9’s involvement in transcriptional addiction in cancer. Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype for which effective targeted therapies remain limited. Here, we aimed to define the therapeutic potential of novel CDK9 inhibitors in TNBC.

methodsWe explored the efficacy and mechanism of action of novel CDK9 inhibitors, alone or in combination with EGFR inhibitors, using TNBC cell lines and in vivo xenograft models.

resultsTargeting CDK9 significantly impaired proliferation and induced apoptosis in multiple TNBC cell lines. Transcriptomic analyses revealed that CDK9 inhibitors induced downregulation of genes involved in transcription, cell cycle progression, and oncogenic signalling pathways, including TGF-β and Wnt/β-catenin signalling. Combined CDK9 and EGFR inhibition disrupted transcriptional programs, enhanced TNBC cell death in vitro, and acted synergistically to reduce tumour growth in PDX and Hs578T xenograft models, although this combination was also associated with increased toxicity.

conclusionOur results position CDK9 as a promising therapeutic target in TNBC, either alone or in combination with EGFR inhibition, provided that side effects associated with this combination treatment can be controlled.

Indexed as

Cyclin-Dependent Kinase 9Protein Kinase InhibitorsTriple Negative Breast NeoplasmsAnimalsApoptosisCell Line, TumorCell ProliferationErbB ReceptorsFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudeXenograft Model Antitumor AssaysCDK9 protein, humanCyclin-Dependent Kinase 9EGFR protein, humanErbB ReceptorsProtein Kinase Inhibitors

Identifiers

PMID41505030
PMCPMC12783313

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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.