Decreased eukaryotic initiation factors expression upon temozolomide treatment-potential novel implications for eIFs in glioma therapy.

Autor: Krassnig S; Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria., Leber SL; Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria.; Division of Neuroradiology, Vascular & Interventional Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9, Graz, 8036, Austria., Orthmann A; EPO Berlin Buch GmbH, Berlin, Germany., Golob-Schwarzl N; Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria.; Center for Biomarker Research in Medicine, Graz, Austria., Huber HJ; Drug Discovery Sciences, Dr. Boehringer Gasse 5-11 A-1121, Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria., Wohlrab C; Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria., Skofler C; Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria.; Center for Biomarker Research in Medicine, Graz, Austria., Pennauer M; Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria., Raicht A; Division of Paediatric Haematology and Oncology, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria., Birkl-Toeglhofer AM; Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria.; Department of Pathology, Medical University of Innsbruck, Müllerstraße 44, Innsbruck, 6020, Austria., Naumann M; Institute of Experimental Internal Medicine, Otto Von Guericke University, Magdeburg, Germany., Mahdy-Ali K; Department of Neurosurgery, Medical University of Graz, Graz, Austria., von Campe G; Department of Neurosurgery, Medical University of Graz, Graz, Austria., Leoni M; Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria., Alcaniz J; EPO Berlin Buch GmbH, Berlin, Germany., Hoffmann J; EPO Berlin Buch GmbH, Berlin, Germany., Wälchli T; Group of CNS Angiogenesis and Neurovascular Link, Neuroscience Center Zurich, Division of Neurosurgery, University and University Hospital Zurich, Zurich, Switzerland.; Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.; Group Brain Vasculature and Perivascular Niche, Division of Experimental and Translational Neuroscience, Krembil Brain Institute, Toronto Western Hospital, University Health Network, Krembil Research Institute, University of Toronto, Toronto, ON, Canada.; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada., Weis S; Division of Neuropathology, Kepler University Hospital, Johannes Kepler University, Neuromed Campus, Linz, Austria., Benesch M; Division of Paediatric Haematology and Oncology, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria., Haybaeck J; Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria. johannes.Haybaeck@tyrolpath.at.; Center for Biomarker Research in Medicine, Graz, Austria. johannes.Haybaeck@tyrolpath.at.; Department of Pathology, Medical University of Innsbruck, Müllerstraße 44, Innsbruck, 6020, Austria. johannes.Haybaeck@tyrolpath.at.; Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. johannes.Haybaeck@tyrolpath.at.; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. johannes.Haybaeck@tyrolpath.at.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2023 Oct; Vol. 165 (1), pp. 91-100. Date of Electronic Publication: 2023 Oct 31.
DOI: 10.1007/s11060-023-04451-y
Abstrakt: Purpose: Since glioma therapy is currently still limited until today, new treatment options for this heterogeneous group of tumours are of great interest. Eukaryotic initiation factors (eIFs) are altered in various cancer entities, including gliomas. The purpose of our study was to evaluate the potential of eIFs as novel targets in glioma treatment.
Methods: We evaluated eIF protein expression and regulation in 22 glioblastoma patient-derived xenografts (GBM PDX) after treatment with established cytostatics and with regards to mutation profile analyses of GBM PDX.
Results: We observed decreased expression of several eIFs upon temozolomide (TMZ) treatment independent from the phosphatidylinositol 3-kinase (PI3K)/ AKT/ mammalian target of the rapamycin (mTOR) signalling pathway. These effects of TMZ treatment were not present in TMZ-resistant PDX. Combination therapy of regorafenib and TMZ re- established the eIF/AKT/mTOR axis.
Conclusion: Our study provides novel insights into chemotherapeutic effects on eIF regulation in gliomas and suggests that eIFs are interesting candidates for future research to improve glioma therapy.
(© 2023. The Author(s).)
Databáze: MEDLINE
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