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
temozolomide. 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
glioblastoma 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.