ArticleTranslational oncology2024
Neratinib plus dasatinib is highly synergistic in HER2-positive breast cancer in vitro and in vivo.
Article in Translational oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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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.
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Who cites it
3 citing papers in PubMed.
- Protein-protein interactions as therapeutic targets in breast cancer: integrated computational and experimental advances, mechanisms and clinical translation.Molecular biology reports · 2026Review
- Intra-tumor heterogeneity-resistant gene signature predicts prognosis and immune infiltration in breast cancer.Frontiers in immunology · 2025Article
- Potential Drug Synergy Through the ERBB2 Pathway in HER2+ Breast Tumors.International journal of molecular sciences · 2024Article
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHER2-targeted therapies have revolutionised the treatment of HER2-positive breast cancer. However, de novo resistance or the emergence of acquired resistance is a persistent clinical problem. Here we report that neratinib, an irreversible pan-HER inhibitor, in combination with the multi-kinase inhibitor dasatinib, currently used to treat certain leukemias, has strong anti-proliferative effects against models of HER2-positive breast cancer that are innately resistant to trastuzumab or have acquired resistance to neratinib.
methodsNeratinib plus dasatinib was examined in a panel of 20 breast cancer cell lines, including HER2-positive, estrogen-receptor-positive, triple negative, and acquired HER2-targeted therapy resistant models. Drug effects on migration and apoptosis induction was evaluated and signaling alterations were determined by reverse phase protein array (RPPA). In vivo efficacy was examined using orthotopically-implanted HCC1954 cells.
resultsSynergy was observed in cell lines innately resistant to trastuzumab, models with acquired resistance to neratinib, and in triple negative breast cancer cell lines. Further investigation showed that neratinib plus dasatinib induced apoptosis and inhibited cell migration to a greater degree than either drug alone. RPPA revealed that the combination caused suppression of key survival signaling through EGFR, Akt, and MAPK inhibition. In vivo, neratinib plus dasatinib was well tolerated and had a prolonged anti-tumor effect against HCC1954 xenografts.
conclusionsThis study provides a strong pre-clinical rationale for the clinical investigation neratinib and dasatinib in HER2+ breast cancer.
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