دورية أكاديمية
EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models.
| العنوان: | EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models. |
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| المؤلفون: | Álvarez-Vázquez A; Department of Biochemistry and Molecular Biology, Neuroscience Institute of Castilla y León (INCyL), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain., San-Segundo L; Centre for Cancer Research-IBMCC (CSIC), IBSAL, Salamanca, Spain., Cerveró-García P; Department of Biochemistry and Molecular Biology, Neuroscience Institute of Castilla y León (INCyL), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain., Flores-Hernández R; Department of Biochemistry and Molecular Biology, Neuroscience Institute of Castilla y León (INCyL), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain., Ollauri-Ibáñez C; Department of Biochemistry and Molecular Biology, Neuroscience Institute of Castilla y León (INCyL), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain., Segura-Collar B; Instituto de investigaciones Biomédicas I+12 (Imas12), Hospital 12 de Octubre, Madrid, Spain., Hubert CG; Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA., Morrison G; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK., Pollard SM; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK., Lathia JD; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA., Sánchez-Gómez P; Neuro-Oncology Unit, Instituto de Salud Carlos III (ISCIII-UFIEC), Madrid, Spain., Tabernero A; Department of Biochemistry and Molecular Biology, Neuroscience Institute of Castilla y León (INCyL), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain. |
| المصدر: | Neuro-oncology [Neuro Oncol] 2024 Jul 05; Vol. 26 (7), pp. 1230-1246. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 100887420 Publication Model: Print Cited Medium: Internet ISSN: 1523-5866 (Electronic) Linking ISSN: 15228517 NLM ISO Abbreviation: Neuro Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2010- : Oxford : Oxford University Press Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub., |
| مواضيع طبية MeSH: | Glioblastoma*/drug therapy , Glioblastoma*/pathology , Glioblastoma*/metabolism , ErbB Receptors*/genetics , ErbB Receptors*/metabolism , Brain Neoplasms*/drug therapy , Brain Neoplasms*/pathology , Brain Neoplasms*/metabolism , Gene Amplification* , Temozolomide*/pharmacology , Xenograft Model Antitumor Assays*, Animals ; Humans ; Mice ; Erlotinib Hydrochloride/pharmacology ; Tumor Cells, Cultured ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/pathology ; Neoplastic Stem Cells/metabolism |
| مستخلص: | Background: Glioblastoma (GBM) commonly displays epidermal growth factor receptor (EGFR) alterations (mainly amplification and EGFRvIII) and TAT-Cx43266-283 is a Src-inhibitory peptide with antitumor properties in preclinical GBM models. Given the link between EGFR and Src, the aim of this study was to explore the role of EGFR in the antitumor effects of TAT-Cx43266-283. Methods: The effect of TAT-Cx43266-283, temozolomide (TMZ), and erlotinib (EGFR inhibitor) was studied in patient-derived GBM stem cells (GSCs) and murine neural stem cells (NSCs) with and without EGFR alterations, in vitro and in vivo. EGFR alterations were analyzed by western blot and fluorescence in situ hybridization in these cells, and compared with Src activity and survival in GBM samples from The Cancer Genome Atlas. Results: The effect of TAT-Cx43266-283 correlated with EGFR alterations in a set of patient-derived GSCs and was stronger than that exerted by TMZ and erlotinib. In fact, TAT-Cx43266-283 only affected NSCs with EGFR alterations, but not healthy NSCs. EGFR alterations correlated with Src activity and poor survival in GBM patients. Finally, tumors generated from NSCs with EGFR alterations showed a decrease in growth, invasiveness, and vascularization after treatment with TAT-Cx43266-283, which enhanced the survival of immunocompetent mice. Conclusions: Clinically relevant EGFR alterations are predictors of TAT-Cx43266-283 response and part of its mechanism of action, even in TMZ- and erlotinib-resistant GSCs. TAT-Cx43266-283 targets NSCs with GBM-driver mutations, including EGFR alterations, in an immunocompetent GBM model in vivo, suggesting a promising effect on GBM recurrence. Together, this study represents an important step toward the clinical application of TAT-Cx43266-283. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.) |
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| معلومات مُعتمدة: | SA125P20 Junta de Castilla y León; CD21/00080 IBSAL; Instituto de Salud Carlos III; Cleveland Clinic Lerner Research Institute and Case Comprehensive Center; Ministerio de Ciencia e Innovación |
| فهرسة مساهمة: | Keywords: EGFR; NSCs; Src; cell-penetrating peptides; glioblastoma |
| المشرفين على المادة: | EC 2.7.10.1 (ErbB Receptors) EC 2.7.10.1 (EGFR protein, human) YF1K15M17Y (Temozolomide) 0 (epidermal growth factor receptor VIII) DA87705X9K (Erlotinib Hydrochloride) |
| تواريخ الأحداث: | Date Created: 20240320 Date Completed: 20240706 Latest Revision: 20240801 |
| رمز التحديث: | 20240801 |
| مُعرف محوري في PubMed: | PMC11226870 |
| DOI: | 10.1093/neuonc/noae060 |
| PMID: | 38507464 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1523-5866 |
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| DOI: | 10.1093/neuonc/noae060 |