ArticlePloS one2017
MET-EGFR dimerization in lung adenocarcinoma is dependent on EGFR mtations and altered by MET kinase inhibition.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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.
Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- The User's Guide to Amivantamab.Targeted oncology · 2025Review
- Targeting lung cancer with clinically relevant EGFR mutations using anti-EGFR RNA aptamer.Molecular therapy. Nucleic acids · 2023Article
- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- The development of amivantamab for the treatment of non-small cell lung cancer.Respiratory research · 2023Review
- Mass Spectrometry and Pharmacological Approaches to Measuring Cooption and Reciprocal Activation of Receptor Tyrosine Kinases.Proteomes · 2023Article
- Pharmacokinetic/Pharmacodynamic Analysis of Savolitinib plus Osimertinib in an EGFR Mutation-Positive, MET-Amplified Non-Small Cell Lung Cancer Model.Molecular cancer therapeutics · 2023Article
- Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer.The Journal of clinical investigation · 2023Article
- Foretinib Is Effective against Triple-Negative Breast Cancer Cells MDA-MB-231 In Vitro and In Vivo by Down-Regulating p-MET/HGF Signaling.International journal of molecular sciences · 2023Article
- Genotype-determined EGFR-RTK heterodimerization and its effects on drug resistance in lung Cancer treatment revealed by molecular dynamics simulations.BMC molecular and cell biology · 2021Article
- Analysis of transient membrane protein interactions by single-molecule diffusional mobility shift assay.Experimental & molecular medicine · 2021Article
- MET amplification results in heterogeneous responses to osimertinib in EGFR-mutant lung cancer treated with erlotinib.Cancer science · 2020Article
- EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer.Therapeutic advances in medical oncology · 2020Article
- Cell signaling and cancer: a mechanistic insight into drug resistance.Molecular biology reports · 2019Review
- HThe Journal of biological chemistry · 2019Article
- Article
- Inhibitor-induced HER2-HER3 heterodimerisation promotes proliferation through a novel dimer interface.eLife · 2018Article
- [Mechanisms of Resistance to the Third-generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Advanced lung cancer has poor survival with few therapies. EGFR tyrosine kinase inhibitors (TKIs) have high response rates in patients with activating EGFR mutations, but acquired resistance is inevitable. Acquisition of the EGFR T790M mutation causes over 50% of resistance; MET amplification is also common. Preclinical data suggest synergy between MET and EGFR inhibitors. We hypothesized that EGFR-MET dimerization determines response to MET inhibition, depending on EGFR mutation status, independently of MET copy number. We tested this hypothesis by generating isogenic cell lines from NCI-H1975 cells, which co-express L858R and T790M EGFR mutations, namely H1975L858R/T790M (EGFR TKI resistant); H1975L858R (sensitized) and H1975WT (wild-type). We assessed cell proliferation in vitro and tumor growth/stroma formation in derived xenograft models in response to a MET TKI (SGX523) and correlated with EGFR-MET dimerization assessed by Förster Resonance Energy Transfer (FRET). SGX523 significantly reduced H1975L858R/T790M cell proliferation, xenograft tumor growth and decreased ERK phosphorylation. The same was not seen in H1975L858R or H1975WT cells. SGX523 only reduced stroma formation in H1975L858R. SGX523 reduced EGFR-MET dimerization in H1975L858R/T790M but induced dimer formation in H1975L858R with no effect in H1975WT. Our data suggests that MET inhibition by SGX523 and EGFR-MET heterodimerisation are determined by EGFR genotype. As tumor behaviour is modulated by this interaction, this could determine treatment efficacy.
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Registered trials
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.