ArticleCancers2010
Targeting of Both the c-Met and EGFR Pathways Results in Additive Inhibition of Lung Tumorigenesis in Transgenic Mice.
Article in Cancers, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
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
24 citing papers in PubMed, 35 citations in OpenAlex.
- Trial
- Lung cancer: Animal model of lung cancer, molecular carcinogenesis of lung cancer, and antitumor effect ofOpen veterinary journal · 2025Review
- Design, Synthesis and Biological Evaluation of Multi-Target Anti-Cancer Agent PYR26.International journal of molecular sciences · 2023Article
- Modeling restoration of gefitinib efficacy by co-administration of MET inhibitors in an EGFR inhibitor-resistant NSCLC xenograft model: A tumor-in-host DEB-based approach.CPT: pharmacometrics & systems pharmacology · 2021Article
- Aberrant expression of the UPF1 RNA surveillance gene disturbs keratinocyte homeostasis by stabilizing AREG.International journal of molecular medicine · 2020Article
- Dual-targeted NIS polyplexes-a theranostic strategy toward tumors with heterogeneous receptor expression.Gene therapy · 2019Article
- Phase 1b Trial of Ficlatuzumab, a Humanized Hepatocyte Growth Factor Inhibitory Monoclonal Antibody, in Combination With Gefitinib in Asian Patients With NSCLC.Clinical pharmacology in drug development · 2018Article
- Synergistic antitumor activity of low-dose c-Met tyrosine kinase inhibitor and sorafenib on human non-small cell lung cancer cells.Oncology letters · 2018Article
- Combination Strategies Using EGFR-TKi in NSCLC Therapy: Learning from the Gap between Pre-Clinical Results and Clinical Outcomes.International journal of biological sciences · 2018Review
- Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment.Cancers · 2017Review
- Review
- Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Ezrin Enhances EGFR Signaling and Modulates Erlotinib Sensitivity in Non-Small Cell Lung Cancer Cells.Neoplasia (New York, N.Y.) · 2016Article
- Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF).The Journal of biological chemistry · 2015Article
- Mesenchymal Stem Cells Shed Amphiregulin at the Surface of Lung Carcinoma Cells in a Juxtacrine Manner.Neoplasia (New York, N.Y.) · 2015Article
- Molecularly targeted therapies in non-small-cell lung cancer annual update 2014.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2015Article
- Co-targeting c-Met and COX-2 leads to enhanced inhibition of lung tumorigenesis in a murine model with heightened airway HGF.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2014Article
- Phosphoproteomic analysis identifies activated MET-axis PI3K/AKT and MAPK/ERK in lapatinib-resistant cancer cell line.Experimental & molecular medicine · 2013Article
- The role of MET receptor tyrosine kinase in non-small cell lung cancer and clinical development of targeted anti-MET agents.The oncologist · 2013Review
- Lack of association of C-Met-N375S sequence variant with lung cancer susceptibility and prognosis.International journal of medical sciences · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
EGFR and c-Met are both overexpressed in lung cancer and initiate similar downstream signaling, which may be redundant. To determine how frequently ligands that initiate signaling of both pathways are found in lung cancer, we analyzed serum for hepatocyte growth factor (HGF), transforming growth factor-alpha, and amphiregulin (AREG) in lung cancer cases and tobacco-exposed controls. HGF and AREG were both significantly elevated in cases compared to controls, suggesting that both HGF/c-Met and AREG/EGFR pathways are frequently active. When both HGF and AREG are present in vitro, downstream signaling to MAPK and Akt in non-small cell lung cancer (NSCLC) cells can only be completely inhibited by targeting both pathways. To test if dual blockade of the pathways could better suppress lung tumorigenesis in an animal model than single blockade, mice transgenic for airway expression of human HGF were treated with inhibitors of both pathways alone and in combination after exposure to a tobacco carcinogen. Mean tumor number in the group using both the HGF neutralizing antibody L2G7 and the EGFR inhibitor gefitinib was significantly lower than with single agents. A higher tumor K-ras mutation rate was observed with L2G7 alone compared to controls, suggesting that agents targeting HGF may be less effective against mutated K-ras lung tumors. This was not observed with combination treatment. A small molecule c-Met inhibitor decreased formation of both K-ras wild-type and mutant tumors and showed additive anti-tumor effects when combined with gefitinib. Dual targeting of c-Met/EGFR may have clinical benefit for lung cancer.
Identifiers
What OpenQuestion holds
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.