ArticleInternational journal of molecular sciences2021
EphB4 as a Novel Target for the EGFR-Independent Suppressive Effects of Osimertinib on Cell Cycle Progression in Non-Small Cell Lung Cancer.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Rational Design, Synthesis, Biological Evaluation, and In Silico Study of N-Cinnamamide/Benzamide-(4-(Substituted Phenyl)-6-(4-Cyclohexylphenyl)pyrimidin-2-Yl) Derivatives as EGFR Inhibitors Targeting EGFRChemical biology & drug design · 2026Article
- Association of TP53 gain-of-function mutations with early osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma.ESMO open · 2026Article
- Bispecific Ligand-Based EphB4 CAR-T Cells Generated Using Ephrin-B2 Show Potent Antitumor Activity Against Lung Adenocarcinoma.Cancer science · 2026Article
- LUADnet: a deep learning model for prediction of clinical outcomes in lung adenocarcinoma based on gene expression signatures.Translational lung cancer research · 2026Article
- Pulmonary Delivery of Inhalable Sustained Release Nanocomposites Microparticles Encapsulating Osimertinib for Non-Small Cell Lung Cancer Therapy.Pharmaceutics · 2026Article
- Kang Ru Plus reverses osimertinib resistance in lung adenocarcinoma via suppression of EGFR/PI3K/AKT signaling.American journal of cancer research · 2026Article
- Article
- May EPH/Ephrin Targeting Revolutionize Lung Cancer Treatment?International journal of molecular sciences · 2022Review
- Anti-EGF nanobodies enhance the antitumoral effect of osimertinib and overcome resistance in non-small cell lung cancer (NSCLC) cellular models.Medical oncology (Northwood, London, England) · 2022Article
- EphrinB2-EphB4 Signaling in Neurooncological Disease.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osimertinib is the latest generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor used for patients with EGFR-mutated non-small cell lung cancer (NSCLC). We aimed to explore the novel mechanisms of osimertinib by particularly focusing on EGFR-independent effects, which have not been well characterized. We explored the EGFR-independent effects of osimertinib on cell proliferation using NSCLC cell lines, an antibody array analysis, and the association between the action of osimertinib and the ephrin receptor B4 (EphB4). We also studied the clinicopathological significance of EphB4 in 84 lung adenocarcinoma patients. Osimertinib exerted significant inhibitory effects on cell growth and cell cycle progression by promoting the phosphorylation of p53 and p21 and decreasing cyclin D1 expression independently of EGFR. EphB4 was significantly suppressed by osimertinib and promoted cell growth and sensitivity to osimertinib. The EphB4 status in carcinoma cells was positively correlated with tumor size, T factor, and Ki-67 labeling index in all patients and was associated with poor relapse-free survival in EGFR mutation-positive patients. EphB4 is associated with the EGFR-independent suppressive effects of osimertinib on cell cycle and with a poor clinical outcome. Osimertinib can exert significant growth inhibitory effects in EGFR-mutated NSCLC patients with a high EphB4 status.
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