ArticleMolecular cancer therapeutics2018
Molecular Basis for Necitumumab Inhibition of EGFR Variants Associated with Acquired Cetuximab Resistance.
Article in Molecular cancer therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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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.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Pharmacovigilance analysis of cutaneous adverse drug reactions for cetuximab, panitumumab, and necitumumab based on EudraVigilance and WHO VigiAccess.Frontiers in pharmacology · 2026Article
- An Overview of Target Membrane Proteins for Near-Infrared Photoimmunotherapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Microbial riboflavin inhibits ceramide synthase 3 to lower ceramide (d18:1/26:0) and delay colorectal cancer progression.Cell metabolism · 2025Article
- Analysis of EGFR binding hotspots for design of new EGFR inhibitory biologics.Protein science : a publication of the Protein Society · 2024Review
- An engineering strategy to target activated EGFR with CAR T cells.Cell reports methods · 2024Article
- Multivalent Rhamnose-Modified EGFR-Targeting Nanobody Gains Enhanced Innate Fc Effector Immunity and Overcomes Cetuximab Resistance via Recruitment of Endogenous Antibodies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- Mechanisms of Action and Limitations of Monoclonal Antibodies and Single Chain Fragment Variable (scFv) in the Treatment of Cancer.Biomedicines · 2023Review
- Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.World journal of gastroenterology · 2023Review
- Structure-free antibody paratope similarity prediction foriScience · 2023Article
- Resistance to targeted therapy in metastatic colorectal cancer: Current status and new developments.World journal of gastroenterology · 2023Review
- Modeling of Protein Complexes.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling.Frontiers in pharmacology · 2023Review
- Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021.Journal of hematology & oncology · 2022Review
- Identification of Activating Mutations in the Transmembrane and Extracellular Domains of EGFR.Biochemistry · 2022Article
- Therapeutic high affinity T cell receptor targeting a KRASNature communications · 2022Article
- Structure-guided and phage-assisted evolution of a therapeutic anti-EGFR antibody to reverse acquired resistance.Nature communications · 2022Article
- Review
- EGFR R521K Polymorphism Is Not a Major Determinant of Clinical Cetuximab Resistance in Head and Neck Cancer.Cancers · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Acquired resistance to cetuximab, an antibody that targets the EGFR, impacts clinical benefit in head and neck, and colorectal cancers. One of the mechanisms of resistance to cetuximab is the acquisition of mutations that map to the cetuximab epitope on EGFR and prevent drug binding. We find that necitumumab, another FDA-approved EGFR antibody, can bind to EGFR that harbors the most common cetuximab-resistant substitution, S468R (or S492R, depending on the amino acid numbering system). We determined an X-ray crystal structure to 2.8 Å resolution of the necitumumab Fab bound to an S468R variant of EGFR domain III. The arginine is accommodated in a large, preexisting cavity in the necitumumab paratope. We predict that this paratope shape will be permissive to other epitope substitutions, and show that necitumumab binds to most cetuximab- and panitumumab-resistant EGFR variants. We find that a simple computational approach can predict with high success which EGFR epitope substitutions abrogate antibody binding. This computational method will be valuable to determine whether necitumumab will bind to EGFR as new epitope resistance variants are identified. This method could also be useful for rapid evaluation of the effect on binding of alterations in other antibody/antigen interfaces. Together, these data suggest that necitumumab may be active in patients who are resistant to cetuximab or panitumumab through EGFR epitope mutation. Furthermore, our analysis leads us to speculate that antibodies with large paratope cavities may be less susceptible to resistance due to mutations mapping to the antigen epitope.
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Registered trials
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