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Cited by 279Glioma Diagnosis and TreatmentPARP inhibition in cancer therapyCancer therapeutics and mechanisms

Temozolomide and Other Alkylating Agents in Glioblastoma Therapy

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Strobel, Hannah, Baisch, Tim, Fitzel, Rahel, Schilberg, Katharina, Siegelin, Markus D., Karpel-Massler, Georg, Debatin, Klaus-Michael, Westhoff, Mike-Andrew·2019·Biomedicines
DOI 10.3390/biomedicines7030069PMC PMC6783999
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Abstract

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.

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Cited by

Sorted by citations

Authors
Strobel, H., Baisch, T., Fitzel, R., Schilberg, K., Siegelin, M. D., Karpel-Massler, G., Debatin, K.-M., & Westhoff, M.-A.
Affiliations
  • Universität Ulm (DE)
  • Columbia University Irving Medical Center (US)
  • Department of Neurosurgery, University Medical Center Ulm, D-89081 Ulm, Germany
Corresponding author
Westhoff, Mike-Andrew
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2019-09-09
Volume
7
Issue
3
Pages
69
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines7030069
PMC
PMC6783999
OpenAlex
W2972376636
Cited by
279
References
2
Citations by year
2026: 24 · 2025: 45 · 2024: 45 · 2023: 41 · 2022: 43 · 2021: 50 · 2020: 28 · 2019: 3
FWCI
3.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Universität Ulm
Topics
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
Keywords
temozolomide, glioblastoma, alkylating agents, DNA alkylation, blood-brain barrier, maximal safe resection, focal radiotherapy, drug resistance, DNA repair, drug interactions, tumor microenvironment

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