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Treatment Considerations for MGMT-Unmethylated Glioblastoma

  • Neuro-Oncology (LE Abrey, Section Editor)
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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 MGMT promoter is methylated, impairing the repair mechanism and conferring chemosensitivity. However, MGMT is overexpressed in 60 % of glioblastomas providing an inherent resistance to alkylating agents and challenging the role of temozolomide in this population. This article reviews the data establishing MGMT promoter methylation as a prognostic factor in glioblastoma and its potential role as a predictor of temozolomide response. It focuses on results from recent studies in newly diagnosed glioblastoma, and the role of temozolomide in MGMT-unmethylated patients. We then turn the discussion to alternatives to temozolomide for newly diagnosed patients as well as therapeutic options at the time of recurrence.

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Conflict of Interest

Jennie W. Taylor declare no conflict of interest.

David Schiff has received paid travel and accommodations from Merck to speak in a symposium about glioma.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of California, San Francisco, CA, USA

    Jennie W. Taylor

  2. Division of Neuro-Oncology, Department of Neurology, University of Virginia, 1300 Jefferson Park Ave #6228, Charlottesville, VA, 22903, USA

    David Schiff

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  1. Jennie W. Taylor
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Correspondence to David Schiff.

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This article is part of the Topical Collection on Neuro-Oncology

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Taylor, J.W., Schiff, D. Treatment Considerations for MGMT-Unmethylated Glioblastoma. Curr Neurol Neurosci Rep 15, 507 (2015). https://doi.org/10.1007/s11910-014-0507-z

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