Evidence map›Paper›PMID 36008466›Full record

ArticleOncogene2022

A high-throughput drug screen reveals means to differentiate triple-negative breast cancer.

Milica Vulin, Charly Jehanno, Atul Sethi, Ana Luísa Correia, Milan M S Obradović, Joana Pinto Couto, Marie-May Coissieux, Maren Diepenbruck, Bogdan-Tiberius Preca, Katrin Volkmann and 19 more

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

Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
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  7. Development of Resistance to Type II JAK2 Inhibitors in MPN Depends on AXL Kinase and Is Targetable.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  8. Cellular plasticity in the breast cancer ecosystem.Upsala journal of medical sciences · 2024
    Review
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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

29 authors at 5 institutions in 1 country.

Milica VulinDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-7686-5102
Charly JehannoDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Atul SethiDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Ana Luísa CorreiaDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Milan M S ObradovićDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Joana Pinto CoutoDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Marie-May CoissieuxDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Maren DiepenbruckDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Bogdan-Tiberius PrecaDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Katrin VolkmannDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Priska Auf der MaurDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-9059-8979
Alexander SchmidtProteomics Core Facility, Biozentrum, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-3149-2381
Simone MünstInstitute of Pathology and Medical Genetics, University Hospital Basel, University of Basel, Basel, Switzerland.
Loïc SauteurDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-9163-0424
Michal KlocDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-4575-7723
Marta PalafoxDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Adrian BritschgiFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Vincent UnterreinerNovartis Institutes for Biomedical Research, Basel, Switzerland.
Olaf GalubaNovartis Institutes for Biomedical Research, Basel, Switzerland.
Isabelle ClaerrNovartis Institutes for Biomedical Research, Basel, Switzerland.
Sandra Lopez-RomeroNovartis Institutes for Biomedical Research, Basel, Switzerland.
Giorgio G GalliNovartis Institutes for Biomedical Research, Basel, Switzerland.ORCID http://orcid.org/0000-0002-9401-060X
Daniel BaeschlinNovartis Institutes for Biomedical Research, Basel, Switzerland.
Ryoko OkamotoDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Savas D SoysalDepartment of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Robert MecheraDepartment of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Walter P WeberDepartment of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
Thomas RadimerskiNovartis Institutes for Biomedical Research, Basel, Switzerland.
Mohamed Bentires-AljDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of Basel, Basel, Switzerland. m.bentires-alj@unibas.ch.ORCID http://orcid.org/0000-0001-6344-1127
University of Basel · CHNovartis (Switzerland) · CHSIB Swiss Institute of Bioinformatics · CHFriedrich Miescher Institute · CHUniversity Hospital of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Plasticity delineates cancer subtypes with more or less favourable outcomes. In breast cancer, the subtype triple-negative lacks expression of major differentiation markers, e.g., estrogen receptor α (ERα), and its high cellular plasticity results in greater aggressiveness and poorer prognosis than other subtypes. Whether plasticity itself represents a potential vulnerability of cancer cells is not clear. However, we show here that cancer cell plasticity can be exploited to differentiate triple-negative breast cancer (TNBC). Using a high-throughput imaging-based reporter drug screen with 9 501 compounds, we have identified three polo-like kinase 1 (PLK1) inhibitors as major inducers of ERα protein expression and downstream activity in TNBC cells. PLK1 inhibition upregulates a cell differentiation program characterized by increased DNA damage, mitotic arrest, and ultimately cell death. Furthermore, cells surviving PLK1 inhibition have decreased tumorigenic potential, and targeting PLK1 in already established tumours reduces tumour growth both in cell line- and patient-derived xenograft models. In addition, the upregulation of genes upon PLK1 inhibition correlates with their expression in normal breast tissue and with better overall survival in breast cancer patients. Our results indicate that differentiation therapy based on PLK1 inhibition is a potential alternative strategy to treat TNBC.

Indexed as

Triple Negative Breast NeoplasmsBreastCell Cycle ProteinsCell Line, TumorCell ProliferationEstrogen Receptor alphaHumansCell Cycle ProteinsEstrogen Receptor alpha

Identifiers

PMID36008466
PMCPMC9507968
OpenAlexW4293088431

What OpenQuestion holds

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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.