Evidence map›Paper›PMID 32686903›Full record

ArticleJournal of cellular and molecular medicine2020

Inhibition of c-MET increases the antitumour activity of PARP inhibitors in gastric cancer models.

Evangelos Koustas, Michalis V Karamouzis, Panagiotis Sarantis, Dimitrios Schizas, Athanasios G Papavassiliou

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

Article in Journal of cellular and molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.8field-weighted citation impact, top 25% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

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  13. PARP inhibitors in gastric cancer: beacon of hope.Journal of experimental & clinical cancer research : CR · 2021
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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

5 authors at 1 institution in 1 country.

Evangelos KoustasMolecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Michalis V KaramouzisMolecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Panagiotis SarantisMolecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Dimitrios SchizasFirst Department of Surgery, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Athanasios G PapavassiliouMolecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0000-0001-5803-4527
National and Kapodistrian University of Athens · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. Activation of c-MET increases tumour cell survival through the initiation of the DNA damage repair pathway. PARP is an essential key in the DNA damage repair pathway. The primary role of PARP is to detect and initiate an immediate cellular response to single-strand DNA breaks. Tumours suppressor genes such as BRCA1/2 are closely associated with the DNA repair pathway. In BRCA1/2 mutations or deficiency status, cells are more likely to develop additional genetic alterations and chromosomal instability and can lead to cancer. In this study, we investigate the role of c-MET and PARP inhibition in a gastric cancer model. We exploited functional in vitro and in vivo experiments to assess the antitumour potential of co-inhibition of c-MET (SU11274) and PARP (NU1025). This leads to a reduction of gastric cancer cells viability, especially after knockdown of BRCA1/2 through apoptosis and induction of γ-Η2ΑΧ. Moreover, in AGS xenograft models, the combinatorial treatment of NU1025 plus SU11274 reduced tumour growth and triggers apoptosis. Collectively, our data may represent a new therapeutic approach for GC thought co-inhibition of c-MET and PARP, especially for patients with BRCA1/2 deficiency tumours.

Indexed as

Models, BiologicalAnimalsAntineoplastic AgentsApoptosisCell Line, TumorClone CellsDNA DamageHistonesHumansIndolesMiceNeoplasm ProteinsPiperazinesPoly(ADP-ribose) Polymerase InhibitorsProto-Oncogene Proteins c-metQuinazolines((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide)Antineoplastic AgentsH2AX protein, humanHistonesIndolesNeoplasm ProteinsNU 1025PiperazinesPoly(ADP-ribose) Polymerase InhibitorsProto-Oncogene Proteins c-metQuinazolinesSulfonamidesBRCA1BRCA2c-Met inhibitorgastric cancerPARP inhibitor

Identifiers

PMID32686903
PMCPMC7521333
OpenAlexW3044867089

What OpenQuestion holds

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LicenceCC BY
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.