ArticleCancer discovery2022
Zenocutuzumab, a HER2xHER3 Bispecific Antibody, Is Effective Therapy for Tumors Driven by NRG1 Gene Rearrangements.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
What it found
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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
116 citing papers in PubMed, 156 citations in OpenAlex.
- Efficacy of Zenocutuzumab inThe New England journal of medicine · 2025Trial
- NRG1 fusions in non-small cell lung cancer: biology, diagnostics, and emerging HER2/HER3 therapies-a narrative review.Translational lung cancer research · 2026Review
- Bispecific antibodies for cancer therapy: evolution of structural formats and co-targeting strategies from wet-lab to AI-driven in silico modeling.Cancer letters · 2026Review
- Article
- Bispecific Antibodies in Solid Tumors: Mechanistic Insights, Clinical Advances, and Future Directions.Journal of immunotherapy and precision oncology · 2026Review
- Targeting fusion proteins in solid tumors: from oncogenic mechanisms to clinical interventions.Acta pharmacologica Sinica · 2026Review
- Pancreatic cancer.Nature reviews. Disease primers · 2026Review
- Structure, mechanism and clinical relevance of NRG1 fusions in cancer.Journal of biomedical science · 2026Review
- Targeting Tumor Microenvironment-Derived NRG1-HER2/3 Signaling with Zenocutuzumab Restores Sensitivity to AR Inhibition in PTEN Wild-type Prostate Cancer.Molecular cancer therapeutics · 2026Article
- COLEC12high tumor-associated macrophages orchestrate lenvatinib resistance and cancer stemness in hepatocellular carcinoma via paracrine NRG1-HER2/HER3 signaling.Clinical and molecular hepatology · 2026Article
- Roles of Her3 in carcinogenesis and advances in Her3-targeted cancer therapy.Discover oncology · 2026Review
- Efficacy and safety of approved cellular therapies and bispecific antibodies in solid tumors: the current state.Discover oncology · 2026Review
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Characterizing the molecular and clinical implications of NRG1 fusions in NSCLC through integrated RNA and DNA sequencing analysis.European journal of medical research · 2026Article
- Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer.Cancer discovery · 2026Article
- Mechanism of Bispecific Antibodies and Clinical Research Advances in Lung Cancer.Current cancer drug targets · 2026Review
- Monoclonal Antibodies and Derivatives: Therapeutic Tools for Cancer.Oncology research · 2026Review
- Gastrointestinal cancer: molecular pathogenesis and targeted therapy.Molecular biomedicine · 2025Review
- TNFR2/CCR8 bispecific antibody enhances antitumor activity through depleting Ti-Tregs and boosting effector CD8Oncoimmunology · 2025Article
- Review
56 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
22 authors at 2 institutions in 2 countries.
Funding
Abstract
NRG1 rearrangements are recurrent oncogenic drivers in solid tumors. NRG1 binds to HER3, leading to heterodimerization with other HER/ERBB kinases, increased downstream signaling, and tumorigenesis. Targeting ERBBs, therefore, represents a therapeutic strategy for these cancers. We investigated zenocutuzumab (Zeno; MCLA-128), an antibody-dependent cellular cytotoxicity-enhanced anti-HER2xHER3 bispecific antibody, in NRG1 fusion-positive isogenic and patient-derived cell lines and xenograft models. Zeno inhibited HER3 and AKT phosphorylation, induced expression of apoptosis markers, and inhibited growth. Three patients with chemotherapy-resistant NRG1 fusion-positive metastatic cancer were treated with Zeno. Two patients with ATP1B1-NRG1-positive pancreatic cancer achieved rapid symptomatic, biomarker, and radiographic responses and remained on treatment for over 12 months. A patient with CD74-NRG1-positive non-small cell lung cancer who had progressed on six prior lines of systemic therapy, including afatinib, responded rapidly to treatment with a partial response. Targeting HER2 and HER3 simultaneously with Zeno is a novel therapeutic paradigm for patients with NRG1 fusion-positive cancers. SIGNIFICANCE: NRG1 rearrangements encode chimeric ligands that activate the ERBB receptor tyrosine kinase family. Here we show that targeting HER2 and HER3 simultaneously with the bispecific antibody Zeno leads to durable clinical responses in patients with NRG1 fusion-positive cancers and is thus an effective therapeutic strategy. This article is highlighted in the In This Issue feature, p. 1171.
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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.