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

Abstract:

: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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Fan CH,Liu WL,Cao H,Wen C,Chen L,Jiang G

doi

10.1038/cddis.2013.388

subject

Has Abstract

pub_date

2013-10-24 00:00:00

pages

e876

issn

2041-4889

pii

cddis2013388

journal_volume

4

pub_type

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