Advances in the management of glioblastoma: the role of temozolomide and MGMT testing
نویسندگان
چکیده
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.
منابع مشابه
The role of gene body cytosine modifications in MGMT expression and sensitivity to temozolomide.
The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is known to play a role in sensitivity to temozolomide. Promoter hypermethylation of MGMT is commonly used to predict low expression levels of MGMT in gliomas, despite observed discordance between promoter methylation and protein levels. Here, we investigated the functional role of gene body cytosine modification in regulati...
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Abstract Prognosis for patients with glioblastoma continues to be limited, despite an aggressive, multimodal treatment including alkylating chemotherapy. Temozolomide, the most widely used alkylating agent in glioblastoma, is cytotoxic to cells by inducing DNA damage but can be rapidly repaired by the protein O (6)-methylguanine DNA methyltransferase (MGMT). In a subset of glioblastomas, the MG...
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PURPOSE In the setting of a prospective clinical trial, we determined the predictive value of the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter for outcome in glioblastoma patients treated with the alkylating agent temozolomide. Expression of this excision repair enzyme has been associated with resistance to alkylating chemotherapy. EXPERIMENTAL DESIGN The ...
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Introduction: Glioblastoma multiforme is the most aggressive tumor of the central nervous system. Despite advances in its management, overall prognosis remains poor, with a median survival time of less than one year. Good response to chemotherapy with temozolomide (TMZ) is usually associated with methylation of the promoter of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene. Case Repor...
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عنوان ژورنال:
دوره 5 شماره
صفحات -
تاریخ انتشار 2013