Evidence map›Paper›PMID 24675467›Full record

ArticleCell death & disease2014

Targeting of preexisting and induced breast cancer stem cells with trastuzumab and trastuzumab emtansine (T-DM1).

J Diessner, V Bruttel, R G Stein, E Horn, S F M Häusler, J Dietl, A Hönig, J Wischhusen

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

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.3field-weighted citation impact, top 4% 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

33 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Targeting Breast Cancer Stem Cells Using Naturally Occurring Phytoestrogens.International journal of molecular sciences · 2022
    Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Inhibition of HER2 Increases JAGGED1-dependent Breast Cancer Stem Cells: Role for Membrane JAGGED1.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018
    Article
  17. Fate of Antibody-Drug Conjugates in Cancer Cells.Journal of experimental & clinical cancer research : CR · 2018
    Review
  18. Review
  19. Review
  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

8 authors at 1 institution in 1 country.

J DiessnerDepartment for Obstetrics and Gynecology, University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany.
V BruttelDepartment for Obstetrics and Gynecology, University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany.
R G Stein1] Department for Obstetrics and Gynecology, University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany [2] Else-Kröner Research Training Program for Clinician Scientists, University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany.
E HornDepartment for Obstetrics and Gynecology, University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany.
S F M Häusler1] Department for Obstetrics and Gynecology, University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany [2] Interdisciplinary Center for Clinical Research (IZKF), University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany.
J DietlDepartment for Obstetrics and Gynecology, University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany.
A Hönig1] Department for Obstetrics and Gynecology, University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany [2] Interdisciplinary Center for Clinical Research (IZKF), University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany.
J Wischhusen1] Department for Obstetrics and Gynecology, University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany [2] Interdisciplinary Center for Clinical Research (IZKF), University of Würzburg Medical School, Josef-Schneider-Street 4, Würzburg 97080, Germany.
University of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The antibody trastuzumab (Herceptin) has substantially improved overall survival for patients with aggressive HER2-positive breast cancer. However, about 70% of all treated patients will experience relapse or disease progression. This may be related to an insufficient targeting of the CD44(high)CD24(low) breast cancer stem cell subset, which is not only highly resistant to chemotherapy and radiotherapy but also a poor target for trastuzumab due to low HER2 surface expression. Hence, we explored whether the new antibody-drug conjugate T-DM1, which consists of the potent chemotherapeutic DM1 coupled to trastuzumab, could improve the targeting of these tumor-initiating or metastasis-initiating cells. To this aim, primary HER2-overexpressing tumor cells as well as HER2-positive and HER2-negative breast cancer cell lines were treated with T-DM1, and effects on survival, colony formation, gene and protein expression as well as antibody internalization were assessed. This revealed that CD44(high)CD24(low)HER2(low) stem cell-like breast cancer cells show high endocytic activity and are thus particularly sensitive towards the antibody-drug conjugate T-DM1. Consequently, preexisting CD44(high)CD24(low) cancer stem cells were depleted by concentrations of T-DM1 that did not affect the bulk of the tumor cells. Likewise, colony formation was efficiently suppressed. Moreover, when tumor cells were cocultured with natural killer cells, antibody-dependent cell-mediated cytotoxicity was enhanced, and EMT-mediated induction of stem cell-like properties was prevented in differentiated tumor cells. Thus our study reveals an unanticipated targeting of stem cell-like breast cancer cells by T-DM1 that may contribute to the clinical efficacy of this recently approved antibody-drug conjugate.

Indexed as

Ado-Trastuzumab EmtansineAdultAgedAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, CDAutophagyBreast NeoplasmsCell Line, TumorCell MembraneClone CellsCoculture TechniquesDose-Response Relationship, DrugEndocytosisErb-b2 Receptor Tyrosine KinasesFemaleAdo-Trastuzumab EmtansineAntibodies, Monoclonal, HumanizedAntigens, CDErb-b2 Receptor Tyrosine KinasesMaytansineTrastuzumab

Identifiers

PMID24675467
PMCPMC3973200
OpenAlexW2056298287

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.