ArticleOncogene2019
An HER3-targeting antibody-drug conjugate incorporating a DNA topoisomerase I inhibitor U3-1402 conquers EGFR tyrosine kinase inhibitor-resistant NSCLC.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 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
59 citing papers in PubMed, 99 citations in OpenAlex.
- HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- PARP inhibition enhances the antitumor activity of HER3-DXd in non-small cell lung cancer.Cell reports. Medicine · 2026Article
- The Effect of HER3 Expression on Prognosis in EGFR-Mutant Non-Small Cell Lung Cancer: A Retrospective Real-World Study.Medicina (Kaunas, Lithuania) · 2026Article
- HER3 beyond the canonical paradigm: a versatile signaling hub in oncogenesis and therapeutic resistance.Journal of translational medicine · 2026Review
- HER3-targeting Antibody-drug Conjugates Therapy for Solid Tumors: Recent Advances and Future Potentials.Current medicinal chemistry · 2026Review
- Antibody-drug conjugates in colorectal cancer: advances in targeted delivery and personalized oncology.Frontiers in bioengineering and biotechnology · 2026Review
- Izalontamab (SI-B001), a Novel EGFRxHER3 Bispecific Antibody in Patients with Locally Advanced or Metastatic Epithelial Tumor: Results from First-in-Human Phase I/Ib Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- HERTHENA-PanTumor01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated advanced solid tumors.Future oncology (London, England) · 2025Article
- Patritumab Deruxtecan (HER3-DXd; MK-1022) in Non-Small Cell Lung Cancer After Platinum-Based Chemotherapy and Immunotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Quantitative Protein Expression of Antibody-Drug Conjugate Targets in EGFR Mutated and Wild-type Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Navigating the Landscape of Resistance Mechanisms in Antibody-Drug Conjugates for Cancer Treatment.Targeted oncology · 2025Review
- Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer.International journal of molecular sciences · 2025Review
- Optimizing Osimertinib for NSCLC: Targeting Resistance and Exploring Combination Therapeutics.Cancers · 2025Review
- The Therapeutic Significance of HER3 in Non-small Cell Lung Cancer (NSCLC): A Review Study.Current medicinal chemistry · 2025Review
- The potential of antibody-drug conjugates in immunotherapy for non-small cell lung cancer: current progress and future.Frontiers in oncology · 2025Review
- The Evolving Paradigm of Antibody-Drug Conjugates Targeting the ErbB/HER Family of Receptor Tyrosine Kinases.Pharmaceutics · 2024Review
- Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice.Experimental hematology & oncology · 2024Review
- HER3-targeted therapy: the mechanism of drug resistance and the development of anticancer drugs.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- HER3 is widely expressed across diverse subtypes of NSCLC in a retrospective analysis of archived tissue samples.Future oncology (London, England) · 2024Article
- Predicting Response to Antibody Drug Conjugates: A Focus on Antigens' Targetability.The oncologist · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EGFR tyrosine kinase inhibitors (TKIs) are standard therapy for EGFR-mutant non-small cell lung cancer (NSCLC); however, these tumours eventually acquire chemoresistance. U3-1402 is an anti-HER3 antibody-drug conjugate with a novel topoisomerase I inhibitor, DXd. In the current study, we evaluated the anticancer efficacy of U3-1402 in EGFR-mutant NSCLC cells with acquired resistance to EGFR-TKIs. HCC827GR5 and PC9AZDR7 are EGFR-TKI-resistant clones for gefitinib and osimertinib, respectively. U3-1402 alone or in combination with the EGFR-TKI erlotinib demonstrated potent anticancer efficacy in HCC827GR5 cells using an in vitro growth inhibition assay and in vivo xenograft mouse model. U3-1402 induced apoptosis in HCC827GR5 cells accompanying phosphorylation of histone H2A.X, a marker of DNA damage, but did not block HER3/PI3K/AKT signalling. Further, we found using flow cytometry that the cell surface HER3 expression level in HCC827GR5 cells was twice that found in HCC827 cells, indicating internalization of U3-1402 was increased in resistant cells. In addition, administration of U3-1402 notably repressed growth of EGFR-TKI osimertinib-resistant PC9AZDR7 xenograft tumours, and that PC9AZDR7 cells expressed five times greater cell surface HER3 than PC9 cells. Furthermore, using immunofluorescent microscopy, HER3 was observed predominantly in the nucleus of PC9 cells, but was localized in the cytoplasm of PC9AZDR7 cells. This finding indicates that altered trafficking of the HER3-U3-1402 complex may accelerate linker payload cleavage by cytoplasmic lysosomal enzymes, resulting in DNA damage. Our results indicate that administration of U3-1402 alone or in combination with an EGFR-TKI may have potential as a novel therapy for EGFR-TKI-resistant EGFR-mutant NSCLC.
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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.