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CP-116 Biomarkers associated to treatment response and prognosis in Glioblastoma Multiforme
  1. J Pérez-Morales,
  2. R López-Sepúlveda,
  3. M Cañadas-Garre,
  4. FJ Orantes-Casado de Amezua,
  5. A Madrid-Paredes,
  6. MA Calleja-Hernández
  1. Hospital Universitario Virgen de Las Nieves, Pharmacy, Granada, Spain

Abstract

Background Gliomas are the most common primary brain tumours, accounting for 80% of malignant tumours of the central nervous system. Glioblastoma Multiforme (GBM), a grade IV glioma, is the most aggressive, with an overage overall survival (OS) of 12 months, and the most prevalent, about 60–70% of all gliomas. In recent years, chromosomal, genetic and epigenetic mutations in GBM have been discovered and are under investigation to determinate their role in clinical practice.

Purpose To determine the main biomarkers evaluated for possible clinical utility in GBM.

Materials and methods Literature review of biomarkers associated with treatment response/prognosis in GBM published in 2009 or later in a third or upper quartile in their category.

Results Forty-two articles were reviewed. The main biomarkers identified in gliomas were: mutations involving isocitrate dehydrogenase, 1p/19q deletion status and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Currently, MGMT status is the most acknowledged, being considered a predictive factor for chemotherapy response. The MGMT gene encodes an enzyme that repairs the damage induced by O(6)-alkylating agents, such as temozolomide, an oral chemotherapy drug indicated in primary GBM. About 50% of patients show this promoter methylated in tumoral cells, resulting in low expression of this enzyme. Several studies show higher OS and free survival progression (FSP) in patients with methylated promoter. Patients with unmethylated promoter present a response to radiotherapy plus temozolomide similar to radiotherapy alone, in terms of OS and FSP. The most accepted method of determining promoter status is polymerase chain reaction after extraction of DNA and sodium bisulphite conversion.

Conclusions Biomarkers such as MGMT promoter methylation status could help therapeutic management of GBM patients. Although the role of MGMT promoter methylation status in GBM response to temozolomide is well known, it is not yet taken into account in clinical decision-taking.

No conflict of interest.

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