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Nieto, A.E.* ; Fleischmann, D.F.* ; Unger, K. ; Albrecht, V.* ; Maas, J.* ; Zitzelsberger, H. ; Belka, C. ; Proescholdt, M.* ; Lauber, K. ; Niyazi, M.* ; Orth, M.*

Targeting VEGF-A in an immunocompetent orthotopic mouse model of mesenchymal glioblastoma improves antitumorigenicity and decreases proinflammatory response in normal brain tissue after fractionated radiotherapy.

Adv. Therap. 8:2400374 (2025)
Verlagsversion Forschungsdaten DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Glioblastoma is the most aggressive primary brain tumor characterized by a dismal prognosis and a profound therapy resistance that is most evident for the mesenchymal molecular subtype of glioblastoma. Targeting vascular endothelial growth factor (VEGF)-A by the monoclonal antibody bevacizumab, despite failing to improve survival in randomized trials, yields relevant benefits in glioblastoma patients such as reduction of radionecrosis, an adverse event associated with radiotherapy. This demands for continued research to identify optimal combinations of anti-VEGF-A and standard therapies for glioblastoma treatment. We show here that blocking VEGF-A in an immune competent orthotopic glioblastoma mouse model resembling the adverse mesenchymal molecular subtype increases the tumoricidal effect of computed tomography (CT)-based fractionated radiotherapy and also rectifies irradiation-induced expression of genes with known association to mesenchymal subtype enrichment as revealed by microarray-based transcriptome analyses of explanted tumors. VEGF-A blockade also decreases the expression of myeloid-cell-related gene patterns in irradiated tumors and lowers inflammatory response in normal brain tissue after tumor irradiation. Hence, these data both provide a hint how blockade of VEGF-A increases the effect of radiotherapy in mesenchymal glioblastoma and a mechanistic base for clinical observations reporting reduced incidences of radionecrosis in glioblastoma patients treated with radiotherapy upon concurrent administration of bevacizumab.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Glioblastoma ; Inflammation ; Mesenchymal ; Normal Brain Tissue ; Radiotherapy ; Vegf-a; Phase-ii Trial; Radiation Necrosis; Recurrent Glioblastoma; Gene-expression; Bevacizumab; Reirradiation; Resistance; Therapy; Immune; Glioma
ISSN (print) / ISBN 2366-3987
e-ISSN 2366-3987
Zeitschrift Advanced Therapeutics
Quellenangaben Band: 8, Heft: 2, Seiten: , Artikelnummer: 2400374 Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Translational Metabolic Oncology (IDC-TMO)
Förderungen FoeFoLe program of the medical faculty of the "Ludwig-Maximilians-Universitat" (LMU) Munich, Germany
Projekt DEAL