Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-10599

Wick, W; Platten, M; Weller, M (2009). New (alternative) temozolomide regimens for the treatment of glioma. Neuro-Oncology, 11(1):69-79.

[img]
Preview
PDF
1MB

View at publisher

Abstract

One barrier to successful treatment of malignant glioma is resistance to alkylating agents such as temozolomide. The cytotoxic activity of temozolomide and other alkylating agents is believed to be manifested largely by the formation of O-methylguanine DNA adducts. Consequently, the primary mechanism of resistance to temozolomide is a function of the activity of the DNA repair enzyme O-methylguanine DNA methyltransferase (MGMT). Fortuitously, MGMT is inactivated after each reaction (ie, suicide enzyme). Therefore, if the rate of DNA alkylation were to outpace the rate of MGMT protein synthesis, the enzyme could, in theory, be depleted. Several studies have shown that prolonged exposure to temozolomide can deplete MGMT activity in blood cells, a process that could potentially increase the antitumor activity of the drug. To date, however, there are limited data demonstrating the depletion of MGMT activity in tumor tissue exposed to temozolomide. A variety of dosing schedules that increase the duration of exposure and the cumulative dose of temozolomide are currently being investigated for the treatment of glioma, with the goal of improving antitumor activity and overcoming resistance. These alternative dosing regimens have been shown to deplete MGMT activity in peripheral blood mononuclear cells, but the regimen that provides the best balance between enhanced antitumor activity and acceptable hematologic toxicity has yet to be determined.

Citations

50 citations in Web of Science®
53 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

48 downloads since deposited on 22 Jun 2009
14 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
DDC:610 Medicine & health
Language:English
Date:2009
Deposited On:22 Jun 2009 15:49
Last Modified:27 Nov 2013 21:09
Publisher:Oxford University Press
ISSN:1522-8517
Publisher DOI:10.1215/15228517-2008-078
PubMed ID:18772354

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page