ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2024
HER4 and EGFR Activate Cell Signaling in NRG1 Fusion-Driven Cancers: Implications for HER2-HER3-specific Versus Pan-HER Targeting Strategies.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 17 citations in OpenAlex.
- Efficacy of Zenocutuzumab inThe New England journal of medicine · 2025Trial
- Sonogenetics Nanomedicine Activates the cGAS-STING Pathway for Immunotherapy of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pertuzumab Enhances the Antitumor Activity of T-DXd in HER2-Positive Gastric Cancer Cells.Molecular cancer therapeutics · 2026Article
- Recurrent cancer-associated ERBB4 mutations are transforming and confer resistance to targeted therapies.Molecular oncology · 2026Article
- Article
- Structure, mechanism and clinical relevance of NRG1 fusions in cancer.Journal of biomedical science · 2026Review
- Research Advances in Drug Resistance Mechanisms to Anti-HER2 Therapy in HER2-Positive Breast Cancer.Oncology research · 2026Review
- Article
- Identification of asporin as a HER3 ligand exposes a therapeutic vulnerability in prostate cancer.JCI insight · 2025Article
- Neuregulin-induced HER3 activation drives migration in head and neck squamous cell carcinoma via HER2 and FAK signaling pathways.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb.FEBS open bio · 2025Article
- HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors WithJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- NRG1 Fusions: The New Kid on the Block.Current oncology reports · 2025Review
- Engineering HER2-targeted biparatopic antibodies to promote receptor internalization and restore antitumor efficacy.Frontiers in immunology · 2025Article
- Dysregulated Signaling Pathways in Canine Mammary Tumor and Human Triple Negative Breast Cancer: Advances and Potential Therapeutic Targets.International journal of molecular sciences · 2024Review
- NRG1 Fusions in NSCLC: Being eNRGy Conscious.Lung Cancer (Auckland, N.Z.) · 2024Review
- Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer.Frontiers in oncology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
introductionNRG1 gene fusions are clinically actionable alterations identified in NSCLC and other tumors. Previous studies have reported that NRG1 fusions signal through HER2 and HER3 but, thus far, strategies targeting HER3 specifically or HER2-HER3 signaling have exhibited modest activity in patients with NSCLC bearing NRG1 fusions. Although NRG1 fusion proteins can bind HER4 in addition to HER3, the contribution of HER4 and other HER family members in NRG1 fusion-positive cancers is not fully understood.
methodsWe investigated the role of HER4 and EGFR-HER3 signaling in NRG1 fusion-positive cancers using Ba/F3 models engineered to express various HER family members in combination with NRG1 fusions and in vitro and in vivo models of NRG1 fusion-positive cancer.
resultsWe determined that NRG1 fusions can stimulate downstream signaling and tumor cell growth through HER4, independent of other HER family members. Moreover, EGFR-HER3 signaling is also activated in cells expressing NRG1 fusions, and inhibition of these receptors is also necessary to effectively inhibit tumor cell growth. We observed that cetuximab, an anti-EGFR antibody, in combination with anti-HER2 antibodies, trastuzumab and pertuzumab, yielded a synergistic effect. Furthermore, pan-HER tyrosine kinase inhibitors were more effective than tyrosine kinase inhibitors with greater specificity for EGFR, EGFR-HER2, or HER2-HER4, although the relative degree of dependence on EGFR or HER4 signaling varied between different NRG1 fusion-positive cancers.
conclusionsOur findings indicate that pan-HER inhibition including HER4 and EGFR blockade is more effective than selectively targeting HER3 or HER2-HER3 in NRG1 fusion-positive cancers.
Indexed as
Identifiers
What 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.