Anti-glioma therapy with temozolomide and status of the DNA-repair gene MGMT.
The prognosis of patients with glioblastoma is extremely poor despite multimodal treatments including surgery, chemotherapy and radiotherapy. Recently, the alkylating agent, temozolomide (TMZ) has been shown to improve survival in patients with malignant gliomas, including those with glioblastoma in some clinical studies, and has become one of the standard modalities for treatment of newly diagnosed and recurrent malignant gliomas. The epigenetic silencing of the DNA repair enzyme O(6)-methylguanine-DNA-methyltransferase (MGMT) is the strongest predictive marker for favorable outcome in patients treated with TMZ. However, it remains to be determined how patients with tumors lacking MGMT promoter methylation should be treated. Moreover, even patients with TMZ-sensitive glioblastoma cannot avoid eventual recurrence. In this article, we review the mechanism of the effect of TMZ on tumor cells and resistance to TMZ, and provide an overview of the current management and trials for patients with glioblastoma.
Fukushima
Tsuyoshi
T
Department of Pathology, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. fukuchan@med.miyazaki-u.ac.jp
Takeshima
Hideo
H
Kataoka
Hiroaki
H
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide