ArticleScientific reports2020
Targeting of EGFR by a combination of antibodies mediates unconventional EGFR trafficking and degradation.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 32 citations in OpenAlex.
- Lysosome-Directed Erlotinib Conjugates Reveal Dual Compartment Access and Targeted EGFR Suppression.Chemical & biomedical imaging · 2026Article
- Article
- Resolving the structural basis of therapeutic antibody function in cancer immunotherapy with RESI.Nature communications · 2025Article
- The Agonistic Activity of the Human Epidermal Growth Factor is Reduced by the D46G Substitution.Protein and peptide letters · 2024Article
- ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells.Cancer cell · 2023Article
- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- An Overview of EGFR Mechanisms and Their Implications in Targeted Therapies for Glioblastoma.International journal of molecular sciences · 2023Review
- Delivery of Drugs into Cancer Cells Using Antibody-Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect.Antibodies (Basel, Switzerland) · 2022Review
- Site-Specific Chemoenzymatic Conjugation of High-Affinity M6P Glycan Ligands to Antibodies for Targeted Protein Degradation.ACS chemical biology · 2022Article
- Anti-EGFR Targeted Multifunctional I-131 Radio-Nanotherapeutic for Treating Osteosarcoma: In Vitro 3D Tumor Spheroid Model.Nanomaterials (Basel, Switzerland) · 2022Article
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- Review
- Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells.Cells · 2021Article
- Review
- Erlotinib Promotes Ligand-Induced EGFR Degradation in 3D but Not 2D Cultures of Pancreatic Ductal Adenocarcinoma Cells.Cancers · 2021Article
- Anti-EGFR antibody 528 binds to domain III of EGFR at a site shifted from the cetuximab epitope.Scientific reports · 2021Article
- Updated Insights on EGFR Signaling Pathways in Glioma.International journal of molecular sciences · 2021Review
- KRAS K104 modification affects the KRASScientific reports · 2020Article
- Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Antibody combinations targeting cell surface receptors are a new modality of cancer therapy. The trafficking and signalling mechanisms regulated by such therapeutics are not fully understood but could underlie differential tumour responses. We explored EGFR trafficking upon treatment with the antibody combination Sym004 which has shown promise clinically. Sym004 promoted EGFR endocytosis distinctly from EGF: it was asynchronous, not accompanied by canonical signalling events and involved EGFR clustering within detergent-insoluble plasma mebrane-associated tubules. Sym004 induced lysosomal degradation independently of EGFR ubiquitylation but dependent upon Hrs/Tsg101 that are required for the formation of intraluminal vesicles (ILVs) within late endosomes. We propose Sym004 cross-links EGFR physically triggering EGFR endocytosis and incorporation onto ILVs and so Sym004 sensitivity correlates with EGFR numbers available for binding, rather than specific signalling events. Consistently Sym004 efficacy and potentiation of cisplatin responses correlated with EGFR surface expression in head and neck cancer cells. These findings will have implications in understanding the mode of action of this new class of cancer therapeutics.
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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.