ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Dual blockade of EGFR and c-Met abrogates redundant signaling and proliferation in head and neck carcinoma cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled 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.
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
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Molecular and Clinicopathological Biomarkers Predicting Brain Metastasis in Triple-Negative Breast Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Trial
- Phase II trial of single-agent foretinib (GSK1363089) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.Investigational new drugs · 2013Trial
- Digital Twins for Targeted Therapy in Head and Neck Cancer: From Molecular Stratification to Resistance-Aware Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- ETV4 Promotes Colorectal Cancer Progression by Reprogramming Asparagine Metabolism to Remodel the Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- The MET Oncogene Network of Interacting Cell Surface Proteins.International journal of molecular sciences · 2024Review
- Evaluation of a Novel MET-Targeting Camelid-Derived Antibody in Head and Neck Cancer.Molecular pharmaceutics · 2024Article
- Future investigative directions for novel therapeutic targets in head and neck cancer.Expert review of anticancer therapy · 2024Review
- Crosstalk between CAFs and tumour cells in head and neck cancer.Cell death discovery · 2024Review
- New clinical trial design in precision medicine: discovery, development and direction.Signal transduction and targeted therapy · 2024Review
- Targeted radionuclide therapy for head and neck squamous cell carcinoma: a review.Frontiers in oncology · 2024Review
- Multi-kinase compensation rescues EGFR knockout in a cell line model of head and neck squamous cell carcinoma.Archives of oral biology · 2023Article
- Cbl and Cbl-b independently regulate EGFR through distinct receptor interaction modes.Molecular biology of the cell · 2023Article
- Combinations of EGFR and MET inhibitors reduce proliferation and invasiveness of mucosal melanoma cells.Journal of cellular and molecular medicine · 2023Article
- Review
- Adaptive c-Met-PLXDC2 Signaling Axis Mediates Cancer Stem Cell Plasticity to Confer Radioresistance-associated Aggressiveness in Head and Neck Cancer.Cancer research communications · 2023Article
- EGFR-induced suppression of HPV E6/E7 is mediated by microRNA-9-5p silencing of BRD4 protein in HPV-positive head and neck squamous cell carcinoma.Cell death & disease · 2022Article
- Advances in nuclear medicine-based molecular imaging in head and neck squamous cell carcinoma.Journal of translational medicine · 2022Review
- Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.Head & neck · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeHead and neck squamous cell carcinoma (HNSCC) is usually fatal, and innovative approaches targeting growth pathways are necessary to effectively treat this disease. Both the epidermal growth factor receptor (EGFR) and the hepatocyte growth factor (HGF)/c-Met pathways are overexpressed in HNSCC and initiate similar downstream signaling pathways. c-Met may act in consort with EGFR and/or be activated as a compensatory pathway in the presence of EGFR blockade. EXPERIMENTAL
designExpression levels of EGFR and c-Met were determined by Western analysis in HNSCC cell lines and correlated with antitumor responses to inhibitors of these pathways.
resultsCombining the c-Met inhibitor PF2341066 with the EGFR inhibitor gefitinib abrogated HNSCC cell proliferation, invasion, and wound healing significantly more than inhibition of each pathway alone in HNSCC cell lines. When both HGF and the EGFR ligand, TGF-α, were present in vitro, P-AKT and P-MAPK expression were maximally inhibited by targeting both EGFR and c-Met pathways, suggesting that c-Met or EGFR can compensate when phosphorylation of the other receptor is inhibited. We also showed that TGF-α can induce phosphorylation of c-Met over sixfold by 8 hours in the absence of HGF, supporting a ligand-independent mechanism. Combined targeting of c-Met and EGFR resulted in an enhanced inhibition of tumor volumes accompanied by a decreased number of proliferating cells and increased apoptosis compared with single agent treatment in vivo.
conclusionsTogether, these results suggest that dual blockade of c-Met and EGFR may be a promising clinical therapeutic strategy for treating HNSCC.
Indexed as
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.