ArticleCancer research2013
An antibody that locks HER3 in the inactive conformation inhibits tumor growth driven by HER2 or neuregulin.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Clinical significance of HER2 overexpression in biliary tract carcinoma --a meta analysis.Frontiers in oncology · 2025Pooled it
- The multifaceted roles of receptor tyrosine pseudokinases in cellular signalling.Biochemical Society transactions · 2026Review
- ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging.Cell · 2026Article
- HER3 beyond the canonical paradigm: a versatile signaling hub in oncogenesis and therapeutic resistance.Journal of translational medicine · 2026Review
- Structural analysis of HER2-trastuzumab complex reveals receptor conformational adaptation.Science advances · 2025Article
- HER3: Unmasking a twist in the tale of a previously unsuccessful therapeutic pursuit targeting a key cancer survival pathway.Genes & diseases · 2025Review
- Emerging importance of HER3 in tumorigenesis and cancer therapy.Nature reviews. Clinical oncology · 2025Review
- HER3 receptor and its role in the therapeutic management of metastatic breast cancer.Journal of translational medicine · 2024Review
- SIBP-03, a novel anti-HER3 antibody, exerts antitumor effects and synergizes with EGFR- and HER2-targeted drugs.Acta pharmacologica Sinica · 2024Article
- Review
- HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022Review
- Impairment of IgG Fc functions promotes tumor progression and suppresses NK cell antitumor actions.Communications biology · 2022Article
- Inactivating Amplified HER2: Challenges, Dilemmas, and Future Directions.Cancer research · 2022Article
- Differential tumor inhibitory effects induced by HER3 extracellular subdomain-specific mouse monoclonal antibodies.Cancer chemotherapy and pharmacology · 2022Article
- Targetable HER3 functions driving tumorigenic signaling in HER2-amplified cancers.Cell reports · 2022Article
- Extensive conformational and physical plasticity protects HER2-HER3 tumorigenic signaling.Cell reports · 2022Article
- Targeting ErbB3 Receptor in Cancer with Inhibitory Antibodies from Llama.Biomedicines · 2021Article
- A Phase I Study of Alpelisib in Combination with Trastuzumab and LJM716 in Patients withClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Crystal structures of HER3 extracellular domain 4 in complex with the designed ankyrin-repeat protein D5.Acta crystallographica. Section F, Structural biology communications · 2021Article
- Thirty Years of HER3: From Basic Biology to Therapeutic Interventions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 3 institutions in 2 countries.
Funding
Abstract
HER2/HER3 dimerization resulting from overexpression of HER2 or neuregulin (NRG1) in cancer leads to HER3-mediated oncogenic activation of phosphoinositide 3-kinase (PI3K) signaling. Although ligand-blocking HER3 antibodies inhibit NRG1-driven tumor growth, they are ineffective against HER2-driven tumor growth because HER2 activates HER3 in a ligand-independent manner. In this study, we describe a novel HER3 monoclonal antibody (LJM716) that can neutralize multiple modes of HER3 activation, making it a superior candidate for clinical translation as a therapeutic candidate. LJM716 was a potent inhibitor of HER3/AKT phosphorylation and proliferation in HER2-amplified and NRG1-expressing cancer cells, and it displayed single-agent efficacy in tumor xenograft models. Combining LJM716 with agents that target HER2 or EGFR produced synergistic antitumor activity in vitro and in vivo. In particular, combining LJM716 with trastuzumab produced a more potent inhibition of signaling and cell proliferation than trastuzumab/pertuzumab combinations with similar activity in vivo. To elucidate its mechanism of action, we solved the structure of LJM716 bound to HER3, finding that LJM716 bound to an epitope, within domains 2 and 4, that traps HER3 in an inactive conformation. Taken together, our findings establish that LJM716 possesses a novel mechanism of action that, in combination with HER2- or EGFR-targeted agents, may leverage their clinical efficacy in ErbB-driven cancers.
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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.