Evidence map›Paper›PMID 32318883›Full record

ArticleInvestigational new drugs2020

Targeting c-Met in triple negative breast cancer: preclinical studies using the c-Met inhibitor, Cpd A.

Laura Breen, Patricia B Gaule, Alexandra Canonici, Naomi Walsh, Denis M Collins, Mattia Cremona, Bryan T Hennessy, Michael J Duffy, John Crown, Norma O' Donovan and 1 more

Abstract read
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In one paragraph

Article in Investigational new drugs, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 40% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. 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

11 authors at 5 institutions in 1 country.

Laura BreenMolecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Patricia B GauleMolecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Alexandra CanoniciMolecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Naomi WalshMolecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Denis M CollinsMolecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Mattia CremonaMedical Oncology Group, Department of Molecular Medicine, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland.
Bryan T HennessyMedical Oncology Group, Department of Molecular Medicine, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland.
Michael J DuffyUCD Clinical Research Centre, St. Vincent's University Hospital, Dublin, Ireland.
John CrownMolecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Norma O' DonovanMolecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Alex J EustaceMolecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland. alex.eustace@dcu.ie.
Dublin City University · IEBeaumont Hospital · IERoyal College of Surgeons in Ireland · IESt. Vincent's University Hospital · IEUniversity College Dublin · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction Triple negative breast cancer (TNBC) represents a heterogeneous subtype of breast cancer that carries a poorer prognosis. There remains a need to identify novel drivers of TNBC, which may represent targets to treat the disease. c-Met overexpression is linked with decreased survival and is associated with the basal subtype of breast cancer. Cpd A, a kinase inhibitor selective/specific for Met kinase has demonstrated preclinical anti-cancer efficacy in TNBC. We aimed to assess the anti-cancer efficacy of Cpd A when combined with Src kinase, ErbB-family or hepatocyte growth factor (HGF) inhibitors in TNBC cell lines. Methods We determined the anti-proliferative effects of Cpd A, rilotumumab, neratinib and saracatinib tested alone and in combination in a panel of TNBC cells by acid phosphatase assays. We performed reverse phase protein array analysis of c-Met and IGF1Rβ expression and phosphorylation of c-Met (Y1234/1235) in TNBC cells and correlated their expression/phosphorylation with Cpd A sensitivity. We examined the impact of Cpd A, neratinib and saracatinib tested alone and in combination on invasive potential and colony formation.Results TNBC cells are not inherently sensitive to Cpd A, and neither c-Met expression nor phosphorylation are biomarkers of sensitivity to Cpd A. Cpd A enhanced the anti-proliferative effects of neratinib in vitro; however, this effect was limited to cell lines with innate sensitivity to Cpd A. Cpd A had limited anti-invasive effects but it reduced colony formation in the TNBC cell line panel.Conclusions Despite Cpd A having a potential role in reducing cancer cell metastasis, identification of strong predictive biomarkers of c-Met sensitivity would be essential to the development of a c-Met targeted treatment for an appropriately selected cohort of TNBC patients.

Indexed as

Acid PhosphataseAntineoplastic AgentsCell Line, TumorCell MovementCell ProliferationFemaleHumansProtein Kinase InhibitorsProto-Oncogene Proteins c-metTriple Negative Breast NeoplasmsAcid PhosphataseAntineoplastic AgentsMET protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins c-metc-MetEGFRSrc-kinaseTriple negative breast cancer

Identifiers

PMID32318883
OpenAlexW3016405429

What OpenQuestion holds

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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.