Inhibition of intercellular cytosolic traffic via gap junctions reinforces lomustine-induced toxicity in glioblastoma independent of mgmt promoter methylation status
Schneider M, Potthoff AL, Evert BO, Dicks M, Ehrentraut D, Dolf A, Schmidt EN, Schäfer N, Borger V, Pietsch T, Westhoff MA, Güresir E, Waha A, Vatter H, Heiland DH, Schuss P, Herrlinger U (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 14
Pages Range: 1-13
Article Number: 195
Journal Issue: 3
DOI: 10.3390/ph14030195
Abstract
Glioblastoma is a malignant brain tumor and one of the most lethal cancers in human. Temozolomide constitutes the standard chemotherapeutic agent, but only shows limited efficacy in glioblastoma patients with unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter status. Recently, it has been shown that glioblastoma cells communicate via particular ion-channels—so-called gap junctions. Interestingly, inhibition of these ion channels has been reported to render MGMT promoter-methylated glioblastoma cells more susceptible for a therapy with temozolo-mide. However, given the percentage of about 65% of glioblastoma patients with an unmethylated MGMT promoter methylation status, this treatment strategy is limited to only a minority of glioblas-toma patients. In the present study we show that—in contrast to temozolomide—pharmacological inhibition of intercellular cytosolic traffic via gap junctions reinforces the antitumoral effects of chemotherapeutic agent lomustine, independent of MGMT promoter methylation status. In view of the growing interest of lomustine in glioblastoma first and second line therapy, these findings might provide a clinically-feasible way to profoundly augment chemotherapeutic effects for all glioblastoma patients.
Involved external institutions
Universitätsklinikum Freiburg
Germany (DE)
Universitätsklinikum Bonn
Germany (DE)
Universitätsklinikum Ulm
Germany (DE)
Germany (DE)
Universitätsklinikum Bonn
Germany (DE)
Universitätsklinikum Ulm
Germany (DE)
How to cite
APA:
Schneider, M., Potthoff, A.L., Evert, B.O., Dicks, M., Ehrentraut, D., Dolf, A.,... Herrlinger, U. (2021). Inhibition of intercellular cytosolic traffic via gap junctions reinforces lomustine-induced toxicity in glioblastoma independent of mgmt promoter methylation status. Pharmaceuticals, 14(3), 1-13. https://doi.org/10.3390/ph14030195
MLA:
Schneider, Matthias, et al. "Inhibition of intercellular cytosolic traffic via gap junctions reinforces lomustine-induced toxicity in glioblastoma independent of mgmt promoter methylation status." Pharmaceuticals 14.3 (2021): 1-13.
BibTeX: Download