ArticleNature chemical biology2025
Selective targeting of oncogenic hotspot mutations of the HER2 extracellular domain.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
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Who cites it
6 citing papers in PubMed.
- Protein Engineering-Enabled Cryo-EM Investigation of Small GTPases.Journal of molecular biology · 2026Article
- ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging.Cell · 2026Article
- Endogenous neoantigen-specific antibodies mediate antitumor responses and determine vaccine efficacy.Journal for immunotherapy of cancer · 2026Article
- Reprogramming the SARS-CoV-1 Neutralizing Antibody S230 to SARS-CoV-2 via Directed Evolution and Molecular Docking-Based Binding Mode Analysis.ACS synthetic biology · 2025Article
- Engineering antibody-drug conjugates targeting an adhesion GPCR, CD97.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Novel Humanized Anti-HER3 Antibodies: Structural Characterization and Therapeutic Activity.Antibodies (Basel, Switzerland) · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Oncogenic mutations in the extracellular domain (ECD) of cell-surface receptors could serve as tumor-specific antigens that are accessible to antibody therapeutics. Such mutations have been identified in receptor tyrosine kinases including HER2. However, it is challenging to selectively target a point mutant, while sparing the wild-type protein. Here we developed antibodies selective to HER2 S310F and S310Y, the two most common oncogenic mutations in the HER2 ECD, via combinatorial library screening and structure-guided design. Cryogenic-electron microscopy structures of the HER2 S310F homodimer and an antibody bound to HER2 S310F revealed that these antibodies recognize the mutations in a manner that mimics the dimerization arm of HER2 and thus inhibit HER2 dimerization. These antibodies as T cell engagers selectively killed a HER2 S310F-driven cancer cell line in vitro, and in vivo as a xenograft. These results validate HER2 ECD mutations as actionable therapeutic targets and offer promising candidates toward clinical development.
Indexed as
Identifiers
39438724What 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.