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Predictive Role of O6-Methylguanine DNA Methyltransferase Status for the Treatment of Brain Tumors

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Epigenetics Territory and Cancer

Abstract

Alkylating cytotoxic agents remain a backbone for the systemic therapy of brain tumors. However, the efficacy of temozolomide or other drugs of this class varies dramatically between patients, being negligible in some cases but critical for the disease outcome in others. Search for predictive markers led to discovery of the role of O 6-methylguanine DNA methyltransferase (MGMT), an enzyme involved in the removal of alkyl groups in N7 and O6 positions of guanine. Low expression of MGMT has been repeatedly shown to be associated with the pronounced tumor sensitivity to the systemic treatment. Nevertheless, methodological issues of MGMT status determination remain a subject of investigation. Furthermore, while grade IV malignant gliomas (glioblastomas) have been analyzed with sufficient level of comprehension, there are just a few studies dedicated to less aggressive varieties of CNS malignancies. This chapter presents an update on clinical studies on predictive role of MGMT status.

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Abbreviations

ACNU:

Nimustine

BCNU:

Carmustine

BEV:

Bevacizumab

CBDCA:

Carboplatin

CCNU:

Lomustine

CCRT-TMZ:

Radiotherapy plus temozolomide

CRT:

Chemoradiotherapy

CT:

Chemotherapy

EP:

Etoposide+carboplatin

GKSRS:

Gamma Knife stereotactic radiosurgery

IFNβ:

Human fibroblast interferon

Me:

Methylated

MGMT:

O6-methylguanine-DNA-methyltransferase

mo:

months

MSP:

Methylation-specific polymerase chain reaction

OS:

Overall survival

PAV:

Procarbazine, nimustine, vincristine

PCV:

Procarbazine, lomustine, vincristine

PFS:

Progression free survival

RT:

Radiotherapy

STB:

Stereotactic biopsy

SR:

Surgical resection

TMZ:

Temozolomide

Um:

Unmethylated

VCR:

Vincristine

VP-16:

Etoposide

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Authors and Affiliations

  1. Department of Surgery of the Brain and Spinal Cord, Polenov Research Institute of Neurosurgery, Mayakovskaya 12, 191014, Saint- Petersburg, Russia

    Prof. Marina V. Matsko

  2. Department of Tumor Growth Biology, N N Petrov Institute of Oncology, 197758, Saint- Petersburg, Russia

    Prof. Evgeny N. Imaynitov MD, PhD

Authors
  1. Prof. Marina V. Matsko
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  2. Prof. Evgeny N. Imaynitov MD, PhD
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Correspondence to Marina V. Matsko .

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Editors and Affiliations

  1. Tehran University of Medical Sciences, Department of Medical Genetics School Of Medicine, Tehran, Iran

    Parvin Mehdipour

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Matsko, M., Imaynitov, E. (2015). Predictive Role of O6-Methylguanine DNA Methyltransferase Status for the Treatment of Brain Tumors. In: Mehdipour, P. (eds) Epigenetics Territory and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9639-2_9

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