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Temozolomide in Glioblastoma Therapy: Role of Apoptosis, Senescence and Autophagy. Comment on Strobel et al., Temozolomide and Other Alkylating Agents in Glioblastoma Therapy. Biomedicines 2019, 7, 69
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Temozolomide and Other Alkylating Agents in Glioblastoma Therapy

1
Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, D-89075 Ulm, Germany
2
Faculty of Medicine, Ulm University, D-89081 Ulm, Germany
3
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA
4
Department of Neurosurgery, University Medical Center Ulm, D-89081 Ulm, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomedicines 2019, 7(3), 69; https://doi.org/10.3390/biomedicines7030069
Received: 12 August 2019 / Accepted: 2 September 2019 / Published: 9 September 2019
(This article belongs to the Special Issue Principal Challenges in the Adjuvant Treatment of Glioblastoma)
The alkylating agent temozolomide (TMZ) together with maximal safe bulk resection and focal radiotherapy comprises the standard treatment for glioblastoma (GB), a particularly aggressive and lethal primary brain tumor. GB affects 3.2 in 100,000 people who have an average survival time of around 14 months after presentation. Several key aspects make GB a difficult to treat disease, primarily including the high resistance of tumor cells to cell death-inducing substances or radiation and the combination of the highly invasive nature of the malignancy, i.e., treatment must affect the whole brain, and the protection from drugs of the tumor bulk—or at least of the invading cells—by the blood brain barrier (BBB). TMZ crosses the BBB, but—unlike classic chemotherapeutics—does not induce DNA damage or misalignment of segregating chromosomes directly. It has been described as a DNA alkylating agent, which leads to base mismatches that initiate futile DNA repair cycles; eventually, DNA strand breaks, which in turn induces cell death. However, while much is assumed about the function of TMZ and its mode of action, primary data are actually scarce and often contradictory. To improve GB treatment further, we need to fully understand what TMZ does to the tumor cells and their microenvironment. This is of particular importance, as novel therapeutic approaches are almost always clinically assessed in the presence of standard treatment, i.e., in the presence of TMZ. Therefore, potential pharmacological interactions between TMZ and novel drugs might occur with unforeseeable consequences. View Full-Text
Keywords: temozolomide (TMZ), triazene compounds; alkylating agents; brain tumor; glioblastoma temozolomide (TMZ), triazene compounds; alkylating agents; brain tumor; glioblastoma
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Strobel, H.; Baisch, T.; Fitzel, R.; Schilberg, K.; Siegelin, M.D.; Karpel-Massler, G.; Debatin, K.-M.; Westhoff, M.-A. Temozolomide and Other Alkylating Agents in Glioblastoma Therapy. Biomedicines 2019, 7, 69.

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