ArticlePloS one2017
ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
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- Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates.Cell death discovery · 2025Review
- Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma.International journal of molecular medicine · 2025Article
- Systematic gene expression analysis of putative target genes linked to miR-31 in 83 oral squamous cell carcinoma samples.Head & face medicine · 2025Article
- Targeted radionuclide therapy for head and neck squamous cell carcinoma: a review.Frontiers in oncology · 2024Review
- HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022Review
- Monomethyl auristatin antibody and peptide drug conjugates for trimodal cancer chemo-radio-immunotherapy.Nature communications · 2022Article
- Phase II Trial of CDX-3379 and Cetuximab in Recurrent/Metastatic, HPV-Negative, Cetuximab-Resistant Head and Neck Cancer.Cancers · 2022Article
- AXL regulates neuregulin1 expression leading to cetuximab resistance in head and neck cancer.BMC cancer · 2022Article
- A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.Science (New York, N.Y.) · 2021Article
- A Phase I, First-in-Human Study of GSK2849330, an Anti-HER3 Monoclonal Antibody, in HER3-Expressing Solid Tumors.The oncologist · 2021Article
- Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer.Nature communications · 2021Article
- Neuropeptide bombesin receptor activation stimulates growth of lung cancer cells through HER3 with a MAPK-dependent mechanism.Biochimica et biophysica acta. Molecular cell research · 2020Article
- Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma.Molecular cancer therapeutics · 2019Article
- Molecular and Clinical Activity of CDX-3379, an Anti-ErbB3 Monoclonal Antibody, in Head and Neck Squamous Cell Carcinoma Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Neuregulin‑1 impacting bone marrow mesenchymal stem cell migration is conducive to functional recovery following spinal cord injury.Molecular medicine reports · 2019Article
- Genomic Correlates of Exceptional Response to ErbB3 Inhibition in Head and Neck Squamous Cell Carcinoma.JCO precision oncology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner. We demonstrate that cetuximab treatment primarily inhibits the ERK signaling pathway and KTN3379, an anti-ErbB3 monoclonal antibody, inhibits the AKT signaling pathway, and that dual ErbB receptor inhibition results in enhanced anti-tumor activity in HNSCC models. Surprisingly, we found that while NRG1 is required for ErbB3 activation, it was not sufficient to fully predict for KTN3379 activity. An evaluation of HNSCC patient samples demonstrated that NRG1 expression was significantly associated with expression of the EGFR ligands amphiregulin (AREG) and transforming growth factor α (TGFα). Furthermore, NRG1-positive HNSCC cell lines that secreted high levels of AREG and TGFα or contained high levels of EGFR homodimers (H11D) demonstrated a better response to KTN3379. Although ErbB3 and EGFR activation are uncoupled at the receptor level, their respective signaling pathways are linked through co-expression of their respective ligands. We propose that NRG1 expression and EGFR activation signatures may enrich for improved efficacy of anti-ErbB3 therapeutic mAb approaches when combined with EGFR-targeting therapies in HNSCC.
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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.