ArticleProceedings of the National Academy of Sciences of the United States of America2008
The antibody zalutumumab inhibits epidermal growth factor receptor signaling by limiting intra- and intermolecular flexibility.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 14 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
14 citing papers in PubMed, 53 citations in OpenAlex.
- Single-Molecule 3D Images of "Hole-Hole" IgG1 Homodimers by Individual-Particle Electron Tomography.Scientific reports · 2019Article
- New Therapies in Head and Neck Cancer.Trends in cancer · 2018Review
- Anti-EGFR Agents: Current Status, Forecasts and Future Directions.Targeted oncology · 2016Review
- Polyhedral 3D structure of human plasma very low density lipoproteins by individual particle cryo-electron tomography1.Journal of lipid research · 2016Article
- High-Throughput Screening for Internalizing Antibodies by Homogeneous Fluorescence Imaging of a pH-Activated Probe.Journal of biomolecular screening · 2016Article
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- Rash rates with egfr inhibitors: meta-analysis.Current oncology (Toronto, Ont.) · 2011Article
- Targeted therapy for malignant glioma patients: lessons learned and the road ahead.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2009Review
- Interaction of antibodies with ErbB receptor extracellular regions.Experimental cell research · 2009Review
- Novel human antibody therapeutics: the age of the Umabs.Biotechnology journal · 2008Review
- Review
- Article
- Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET.The Journal of biological chemistryArticle
Corrections and comments
- Retraction · 2012-03-19Author Unresponsive · Error in Analyses · Error in Cell Lines/Tissues · Unreliable Data ·
- Retracted
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epidermal growth factor receptor (EGFR) activates cellular pathways controlling cell proliferation, differentiation, migration, and survival. It thus represents a valid therapeutic target for treating solid cancers. Here, we used an electron microscopy-based technique (Protein Tomography) to study the structural rearrangement accompanying activation and inhibition of native, individual, EGFR molecules. Reconstructed tomograms (3D density maps) showed a level of detail that allowed individual domains to be discerned. Monomeric, resting EGFR ectodomains demonstrated large flexibility, and a number of distinct conformations were observed. In contrast, ligand-activated EGFR complexes were detected only as receptor dimers with ring-like conformations. Zalutumumab, a therapeutic inhibitory EGFR antibody directed against domain III, locked EGFR molecules into a very compact, inactive conformation. Biochemical analyses showed bivalent binding of zalutumumab to provide potent inhibition of EGFR signaling. The structure of EGFR-zalutumumab complexes on the cell surface visualized by Protein Tomography indicates that the cross-linking spatially separates the EGFR molecules' intracellular kinase domains to an extent that appears incompatible with the induction of signaling. These insights into the mechanisms of action of receptor inhibition may also apply to other cell-surface tyrosine kinase receptors of the ErbB family.
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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.