ArticleJournal of experimental & clinical cancer research : CR2019
The third-generation EGFR inhibitor AZD9291 overcomes primary resistance by continuously blocking ERK signaling in glioblastoma.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.International journal of molecular sciences · 2023Pooled it
- Targeting Kinase Signaling in Glioblastoma: Structural Optimization, Blood-Brain Barrier Dynamics and Combinatorial Translational Strategies.International journal of molecular sciences · 2026Review
- RNA-based precision medicine in glioblastoma driven by oncogenic gene fusions.Molecular therapy. Oncology · 2026Review
- Informing development of brain cancer therapies within "preclinical trials" using ex vivo patient tumors.Advanced drug delivery reviews · 2026Review
- Retraction Note: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells.Nature communications · 2025Article
- Astaxanthin is a Novel Candidate for Glioblastoma Treatment? A Review.Current medicinal chemistry · 2025Review
- Development and validation of disulfidptosis-related genes signature for patients with glioma.Discover oncology · 2024Article
- Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy.Brain sciences · 2024Article
- Clinical sequencing reveals diagnostic, therapeutic, and prognostic biomarkers for adult-type diffuse gliomas.Heliyon · 2024Article
- Local therapy in glioma: An evolving paradigm from history to horizons (Review).Oncology letters · 2024Review
- Review
- Targeting drug resistance in glioblastoma (Review).International journal of oncology · 2024Review
- A systematic computational analysis of the endosomal recycling pathway in glioblastoma.Biochemistry and biophysics reports · 2024Article
- Modular Hub Genes in DNA Microarray Suggest Potential Signaling Pathway Interconnectivity in Various Glioma Grades.Biology · 2024Article
- Glioblastoma Therapy: Past, Present and Future.International journal of molecular sciences · 2024Review
- Drug clinical trials on high-grade gliomas: challenges and hopes.Cancer biology & medicine · 2024Article
- Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024Review
- Diagnostic challenges in complicated case of glioblastoma.Pathology oncology research : POR · 2024Article
- Dual blockade of EGFR and PI3K signaling pathways offers a therapeutic strategy for glioblastoma.Cell communication and signaling : CCS · 2023Article
- Normofractionated irradiation and not temozolomide modulates the immunogenic and oncogenic phenotype of human glioblastoma cell lines.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGlioblastoma (GBM) is a fatal brain tumor, lacking effective treatment. Epidermal growth factor receptor (EGFR) is recognized as an attractive target for GBM treatment. However, GBMs have very poor responses to the first- and second-generation EGFR inhibitors. The third-generation EGFR-targeted drug, AZD9291, is a novel and irreversible inhibitor. It is noteworthy that AZD9291 shows excellent blood-brain barrier penetration and has potential for the treatment of brain tumors.
methodsIn this study, we evaluated the anti-tumor activity and effectiveness of AZD9291 in a preclinical GBM model.
resultsAZD9291 showed dose-responsive growth inhibitory activity against six GBM cell lines. Importantly, AZD9291 inhibited GBM cell proliferation > 10 times more efficiently than the first-generation EGFR inhibitors. AZD9291 induced GBM cell cycle arrest and significantly inhibited colony formation, migration, and invasion of GBM cells. In an orthotopic GBM model, AZD9291 treatment significantly inhibited tumor survival and prolonged animal survival. The underlying anti-GBM mechanism of AZD9291 was shown to be different from that of the first-generation EGFR inhibitors. In contrast to erlotinib, AZD9291 continuously and efficiently inhibited the EGFR/ERK signaling in GBM cells.
conclusionAZD9291 demonstrated an efficient preclinical activity in GBM in vitro and in vivo models. AZD9291 has been approved for the treatment of lung cancer with good safety and tolerability. Our results support the possibility of conducting clinical trials of anti-GBM therapy using AZD9291.
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