ArticleMolecular cancer therapeutics2010
ZD6474, a multitargeted inhibitor for receptor tyrosine kinases, suppresses growth of gliomas expressing an epidermal growth factor receptor mutant, EGFRvIII, in the brain.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation of EGFR for the Clinical Treatment of Glioblastoma.Applied biochemistry and biotechnology · 2023Article
- Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma.International journal of molecular sciences · 2018Review
- Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy.Nature genetics · 2018Article
- Genetic biomarkers of drug response for small-molecule therapeutics targeting the RTK/Ras/PI3K, p53 or Rb pathway in glioblastoma.CNS oncology · 2016Review
- Prognostic Value of Dynamic Susceptibility Contrast-Enhanced and Diffusion-Weighted MR Imaging in Patients with Glioblastomas.AJNR. American journal of neuroradiology · 2015Article
- Protein kinase A-dependent phosphorylation of Dock180 at serine residue 1250 is important for glioma growth and invasion stimulated by platelet derived-growth factor receptor α.Neuro-oncology · 2015Article
- EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis.The Journal of clinical investigation · 2014Article
- EGFRvIII stimulates glioma growth and invasion through PKA-dependent serine phosphorylation of Dock180.Oncogene · 2014Article
- Current Understanding on EGFR and Wnt/β-Catenin Signaling in Glioma and Their Possible Crosstalk.Genes & cancer · 2013Review
- Autophagy inhibition induces enhanced proapoptotic effects of ZD6474 in glioblastoma.British journal of cancer · 2013Article
- Activation of Rac1 by Src-dependent phosphorylation of Dock180(Y1811) mediates PDGFRα-stimulated glioma tumorigenesis in mice and humans.The Journal of clinical investigation · 2011Article
- Complex oncogenic signaling networks regulate brain tumor-initiating cells and their progenies: pivotal roles of wild-type EGFR, EGFRvIII mutant and hedgehog cascades and novel multitargeted therapies.Brain pathology (Zurich, Switzerland) · 2011Review
- Delivery of molecularly targeted therapy to malignant glioma, a disease of the whole brain.Expert reviews in molecular medicine · 2011Review
- A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma.Journal of the National Comprehensive Cancer Network : JNCCN · 2011Review
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Epidermal growth factor receptor (EGFR) vIII is a mutated EGFR that is frequently overexpressed in glioblastomas and implicated in response to receptor tyrosine kinase inhibitors. In this study, we investigate the effect of ZD6474 (ZACTIMA, vandetanib), a dual inhibitor for vascular endothelial growth factor receptor 2 and EGFR on growth and angiogenesis of gliomas expressing EGFRvIII. We used two glioma xenograft models, U87MG cells overexpressing EGFRvIII and short-term cultured primary glioma GBM8 cells with EGFRvIII. ZD6474 inhibited tumor growth and angiogenesis and induced cell apoptosis in various brain gliomas. Moreover, significant inhibition of EGFRvIII-expressing U87MG and GBM8 gliomas was observed compared with their controls. Magnetic resonance imaging analysis using the apparent diffusion coefficient and three-dimensional T2*weighed measurements validated ZD6474 inhibition on tumor growth and angiogenesis in EGFRvIII-expressing GBM8 gliomas. Mechanistically, ZD6474 shows better inhibition of cell growth and survival of U87MG/EGFRvIII, GBM6, and GBM8 cells that express EGFRvIII than U87MG or GBM14 cells that have nondetectable EGFRvIII through attenuation of activated phosphorylation of signal transducer and activator of transcription 3, Akt, and Bcl-X(L) expression. Albeit in lesser extent, ZD6474 also displays suppressions of U87MG/EGFR and GBM12 cells that overexpress wild-type EGFR. Additionally, ZD6474 inhibits activation of extracellular signal-regulated kinase 1/2 in both types of cells, and expression of a constitutively active phosphoinositide 3-kinases partially rescued ZD6474 inhibition in U87MG/EGFRvIII cells. Taken together, these data show that ZD6474 significantly inhibited growth and angiogenesis of gliomas expressing EGFRvIII by specifically blocking EGFRvIII-activated signaling mediators, suggesting a potential application of ZD6474 in treatments for glioblastomas that overexpress EGFRvIII. Mol Cancer Ther; 9(4); 929-41. (c)2010 AACR.
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