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Comment in Response to “Temozolomide in Glioblastoma Therapy: Role of Apoptosis, Senescence and Autophagy etc. by B. Kaina”
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Considering the Experimental Use of Temozolomide in Glioblastoma Research

Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, Germany
Department of Biology, School of Sciences and Humanities, Nazarbayev University, Nur-Sultan 010000, Kazakhstan
Department of Gynecology and Obstetrics, Medical Faculty, University Hospital of the Heinrich-Heine-University Duesseldorf, D-40225 Duesseldorf, Germany
Department of Neurosurgery, University Medical Center Ulm, D-89081 Ulm, Germany
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomedicines 2020, 8(6), 151;
Received: 6 May 2020 / Revised: 30 May 2020 / Accepted: 31 May 2020 / Published: 4 June 2020
(This article belongs to the Special Issue Principal Challenges in the Adjuvant Treatment of Glioblastoma)
Temozolomide (TMZ) currently remains the only chemotherapeutic component in the approved treatment scheme for Glioblastoma (GB), the most common primary brain tumour with a dismal patient’s survival prognosis of only ~15 months. While frequently described as an alkylating agent that causes DNA damage and thus—ultimately—cell death, a recent debate has been initiated to re-evaluate the therapeutic role of TMZ in GB. Here, we discuss the experimental use of TMZ and highlight how it differs from its clinical role. Four areas could be identified in which the experimental data is particularly limited in its translational potential: 1. transferring clinical dosing and scheduling to an experimental system and vice versa; 2. the different use of (non-inert) solvent in clinic and laboratory; 3. the limitations of established GB cell lines which only poorly mimic GB tumours; and 4. the limitations of animal models lacking an immune response. Discussing these limitations in a broader biomedical context, we offer suggestions as to how to improve transferability of data. Finally, we highlight an underexplored function of TMZ in modulating the immune system, as an example of where the aforementioned limitations impede the progression of our knowledge. View Full-Text
Keywords: Glioblastoma; limitations of experimental systems; established cell lines; Temozolomide Glioblastoma; limitations of experimental systems; established cell lines; Temozolomide
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Herbener, V.J.; Burster, T.; Goreth, A.; Pruss, M.; von Bandemer, H.; Baisch, T.; Fitzel, R.; Siegelin, M.D.; Karpel-Massler, G.; Debatin, K.-M.; Westhoff, M.-A.; Strobel, H. Considering the Experimental Use of Temozolomide in Glioblastoma Research. Biomedicines 2020, 8, 151.

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