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. 2013:5:1-9.
doi: 10.2147/CPAA.S26586. Epub 2012 Dec 27.

Advances in the management of glioblastoma: the role of temozolomide and MGMT testing

Reena P Thomas  1 , Lawrence Recht, Seema Nagpal
Affiliations

Advances in the management of glioblastoma: the role of temozolomide and MGMT testing

Reena P Thomas et al. Clin Pharmacol. 2013.

Abstract

Glioblastoma (GB) is one of the most lethal forms of cancer, with an invasive growth pattern that requires the use of adjuvant therapies, including chemotherapy and radiation, to prolong survival. Temozolomide (TMZ) is an oral chemotherapy with a limited side effect profile that has become the standard of care in GB treatment. While TMZ has made an impact on survival, tumor recurrence and TMZ resistance remain major challenges. Molecular markers, such as O6-methylguanine-DNA methyltransferase methylation status, can be helpful in predicting tumor response to TMZ, and therefore guides clinical decision making. This review will discuss the epidemiology and possible genetic underpinnings of GB, how TMZ became the standard of care for GB patients, the pharmacology of TMZ, the practical aspects of using TMZ in clinic, and how molecular diagnostics - particularly the use of O6-methylguanine-DNA methyltransferase status - affect clinical management.

Keywords: MGMT; PredictMDx™; glioblastoma; temozolomide.

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Figures

Figure 1
Figure 1
MTIC, the active metabolite of TMZ, adds a methyl group to guanine which causes a base pair mismatch. Notes: This leads either to repair and continued DNA replication, or programed cell death. AGT, the enzyme that repairs damage caused by TMZ, is a “suicide” enzyme (it can be used only once per mismatch repair) and therefore can be overwhelmed. Abbreviations: AGT, O-alkylguanine-DNA alkyltransferase; MGMT, O-methylguanine-DNA methyltransferase; MTIC, 5-(3-methyltriazen-1yl)-imidazole-4-carboxamide; TMZ, temozolomide.
Figure 2
Figure 2
The bisulfite reaction is the first step in detection of MGMT methylation status for both gel-based and real-time polymerase chain reaction. Abbreviation: MGMT, O-methylguanine-DNA methyltransferase.
Figure 3
Figure 3
MGMT status has a significant impact on overall survival in glioblastoma patients. Abbreviation: MGMT, O-methylguanine-DNA methyltransferase.
See this image and copyright information in PMC

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