O6-methylguanine DNA methyltransferase as a promising target for the treatment of temozolomide-resistant gliomas

Temozolomide (TMZ) is an alkylating agent currently used as first-line therapy for gliomas treatment due to its DNA-damaging effect. However, drug resistance occurs, preventing multi-cycle use of this chemotherapeutic agent. One of the major mechanisms of cancer drug resistance is enhanced activity...

Full description

Saved in:
Bibliographic Details
Published in:Cell death & disease 2013-10, Vol.4 (10), p.e876-e876
Main Authors: Fan, C-H, Liu, W-L, Cao, H, Wen, C, Chen, L, Jiang, G
Format: Article
Language:English
Subjects:
631/67/1059/2326
631/67/1059/602
631/67/1922
Animals
Antibodies
Biochemistry
Biomedical and Life Sciences
Brain Neoplasms - drug therapy
Brain Neoplasms - enzymology
Brain Neoplasms - genetics
Cell Biology
Cell Culture
Dacarbazine - analogs & derivatives
Dacarbazine - chemistry
Dacarbazine - pharmacology
Dacarbazine - therapeutic use
Drug Resistance, Neoplasm - drug effects
Glioma - drug therapy
Glioma - enzymology
Glioma - genetics
Humans
Immunology
Life Sciences
Molecular Targeted Therapy
O-Methylguanine-DNA Methyltransferase - antagonists & inhibitors
O-Methylguanine-DNA Methyltransferase - genetics
O-Methylguanine-DNA Methyltransferase - metabolism
Review
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Temozolomide (TMZ) is an alkylating agent currently used as first-line therapy for gliomas treatment due to its DNA-damaging effect. However, drug resistance occurs, preventing multi-cycle use of this chemotherapeutic agent. One of the major mechanisms of cancer drug resistance is enhanced activity of a DNA repair enzyme, O 6 -methylguanine-DNA-methyltransferase (MGMT), which counteracts chemotherapy-induced DNA alkylation and is a key component of chemoresistance. MGMT repairs TMZ-induced DNA lesions, O 6 -meG, by transferring the alkyl group from guanine to a cysteine residue. This review provides an overview of recent advances in the field, with particular emphasis on the inhibitors of MGMT and underlying mechanisms. Literature search was performed through PubMed and all relevant articles were reviewed, with particular attention to MGMT, its role in TMZ-resistant gliomas, effects of MGMT inhibitors and the underlying mechanisms. Several strategies are currently being pursued to improve the therapeutic efficacy of TMZ via inhibition of MGMT to reduce chemoresistance and improve overall survival. MGMT may be a promising target for the treatment of TMZ-resistant gliomas.
ISSN:2041-4889
2041-4889
DOI:10.1038/cddis.2013.388