Dissecting the mechanism of temozolomide resistance and its association with the regulatory roles of intracellular reactive oxygen species in glioblastoma

Chia Hung Chien, Wei Ting Hsueh, Jian Ying Chuang, Kwang Yu Chang

Research output: Contribution to journalReview articlepeer-review

Abstract

Glioblastoma is the most common primary malignant brain tumor that is usually considered fatal even with treatment. This is often a result for tumor to develop resistance. Regarding the standard chemotherapy, the alkylating agent temozolomide is effective in disease control but the recurrence will still occur eventually. The mechanism of the resistance is various, and differs in terms of innate or acquired. To date, aberrations in O6-methylguanine-DNA methyltransferase are the clear factor that determines drug susceptibility. Alterations of the other DNA damage repair genes such as DNA mismatch repair genes are also known to affect the drug effect. Together these genes have roles in the innate resistance, but are not sufficient for explaining the mechanism leading to acquired resistance. Recent identification of specific cellular subsets with features of stem-like cells may have role in this process. The glioma stem-like cells are known for its superior ability in withstanding the drug-induced cytotoxicity, and giving the chance to repopulate the tumor. The mechanism is complicated to administrate cellular protection, such as the enhancing ability against reactive oxygen species and altering energy metabolism, the important steps to survive. In this review, we discuss the possible mechanism for these specific cellular subsets to evade cancer treatment, and the possible impact to the following treatment courses. In addition, we also discuss the possibility that can overcome this obstacle.

Original languageEnglish
Article number18
JournalJournal of Biomedical Science
Volume28
Issue number1
DOIs
Publication statusPublished - Dec 2021

Keywords

  • DNA damage
  • Glioma stem‐like cells
  • Reactive oxygen species
  • Temozolomide resistance

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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