CONSIDERING THE EXPERIMENTAL USE OF TEMOZOLOMIDE IN GLIOBLASTOMA RESEARCH
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Date
2020-06
Authors
Herbener, Verena J.
Burster, Timo
Goreth, Alicia
Pruss, Maximilian
Bandemer, Hélène
Baisch, Tim
Fitzel, Rahel
Siegelin, Markus D.
Karpel-Massler, Georg
Debatin, Klaus-Michael
Journal Title
Journal ISSN
Volume Title
Publisher
Biomedicines
Abstract
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.
Description
Keywords
Type of access: Open Access, Glioblastoma, limitations of experimental systems, established cell lines, Temozolomide
Citation
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. (2020). Considering the Experimental Use of Temozolomide in Glioblastoma Research. Biomedicines, 8(6), 151. https://doi.org/10.3390/biomedicines8060151