Considering the Experimental Use of Temozolomide in Glioblastoma Research
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 damag...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/6/151 |
| _version_ | 1797566133096677376 |
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| author | Verena J. Herbener Timo Burster Alicia Goreth Maximilian Pruss Hélène von Bandemer Tim Baisch Rahel Fitzel Markus D. Siegelin Georg Karpel-Massler Klaus-Michael Debatin Mike-Andrew Westhoff Hannah Strobel |
| author_facet | Verena J. Herbener Timo Burster Alicia Goreth Maximilian Pruss Hélène von Bandemer Tim Baisch Rahel Fitzel Markus D. Siegelin Georg Karpel-Massler Klaus-Michael Debatin Mike-Andrew Westhoff Hannah Strobel |
| author_sort | Verena J. Herbener |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:22:26Z |
| format | Article |
| id | doaj.art-0dbaa97e9f6545918629051de32f143c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T19:22:26Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-0dbaa97e9f6545918629051de32f143c2023-11-20T02:48:14ZengMDPI AGBiomedicines2227-90592020-06-018615110.3390/biomedicines8060151Considering the Experimental Use of Temozolomide in Glioblastoma ResearchVerena J. Herbener0Timo Burster1Alicia Goreth2Maximilian Pruss3Hélène von Bandemer4Tim Baisch5Rahel Fitzel6Markus D. Siegelin7Georg Karpel-Massler8Klaus-Michael Debatin9Mike-Andrew Westhoff10Hannah Strobel11Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, GermanyDepartment of Biology, School of Sciences and Humanities, Nazarbayev University, Nur-Sultan 010000, KazakhstanDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, GermanyDepartment of Gynecology and Obstetrics, Medical Faculty, University Hospital of the Heinrich-Heine-University Duesseldorf, D-40225 Duesseldorf, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, GermanyDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USADepartment of Neurosurgery, University Medical Center Ulm, D-89081 Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, GermanyTemozolomide (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.https://www.mdpi.com/2227-9059/8/6/151Glioblastomalimitations of experimental systemsestablished cell linesTemozolomide |
| spellingShingle | Verena J. Herbener Timo Burster Alicia Goreth Maximilian Pruss Hélène von Bandemer Tim Baisch Rahel Fitzel Markus D. Siegelin Georg Karpel-Massler Klaus-Michael Debatin Mike-Andrew Westhoff Hannah Strobel Considering the Experimental Use of Temozolomide in Glioblastoma Research Biomedicines Glioblastoma limitations of experimental systems established cell lines Temozolomide |
| title | Considering the Experimental Use of Temozolomide in Glioblastoma Research |
| title_full | Considering the Experimental Use of Temozolomide in Glioblastoma Research |
| title_fullStr | Considering the Experimental Use of Temozolomide in Glioblastoma Research |
| title_full_unstemmed | Considering the Experimental Use of Temozolomide in Glioblastoma Research |
| title_short | Considering the Experimental Use of Temozolomide in Glioblastoma Research |
| title_sort | considering the experimental use of temozolomide in glioblastoma research |
| topic | Glioblastoma limitations of experimental systems established cell lines Temozolomide |
| url | https://www.mdpi.com/2227-9059/8/6/151 |
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