MGMT methylation status: the advent of stratified therapy in glioblastoma?
Details
State: Public
Version: author
Serval ID
serval:BIB_C9EA99EBEF3F
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
MGMT methylation status: the advent of stratified therapy in glioblastoma?
Journal
Disease markers
ISSN
0278-0240
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
23
Number
1-2
Pages
97-104
Language
english
Notes
Publication types: Journal Article ; Review - Publication Status: ppublish
Abstract
Glioblastomas are the most malignant gliomas with median survival times of only 15 months despite modern therapies. All standard treatments are palliative. Pathogenetic factors are diverse, hence, stratified treatment plans are warranted considering the molecular heterogeneity among these tumors. However, most patients are treated with "one fits all" standard therapies, many of them with minor response and major toxicities. The integration of clinical and molecular information, now becoming available using new tools such as gene arrays, proteomics, and molecular imaging, will take us to an era where more targeted and effective treatments may be implemented. A first step towards the design of such therapies is the identification of relevant molecular mechanisms driving the aggressive biological behavior of glioblastoma. The accumulation of diverse aberrations in regulatory processes enables tumor cells to bypass the effects of most classical therapies available. Molecular alterations underlying such mechanisms comprise aberrations on the genetic level, such as point mutations of distinct genes, or amplifications and deletions, while others result from epigenetic modifications such as aberrant methylation of CpG islands in the regulatory sequence of genes. Epigenetic silencing of the MGMT gene encoding a DNA repair enzyme was recently found to be of predictive value in a randomized clinical trial for newly diagnosed glioblastoma testing the addition of the alkylating agent temozolomide to standard radiotherapy. Determination of the methylation status of the MGMT promoter may become the first molecular diagnostic tool to identify patients most likely to respond that will allow individually tailored therapy in glioblastoma. To date, the test for the MGMT-methylation status is the only tool available that may direct the choice for alkylating agents in glioblastoma patients, but many others may hopefully become part of an arsenal to stratify patients to respective targeted therapies within the next years.
Keywords
Animals, DNA Modification Methylases, DNA Repair Enzymes, Drug Resistance, Neoplasm, Glioblastoma, Humans, Methylation, Tumor Suppressor Proteins
Pubmed
Web of science
Create date
28/01/2008 9:39
Last modification date
20/08/2019 16:44