Enhanced antitumor efficacy of low-dose Etoposide with oncolytic herpes simplex virus in human glioblastoma stem cell xenografts.

摘要: Purpose: Glioblastoma (GBM) inevitably recurs despite surgery, radiation, and chemotherapy. A subpopulation of tumor cells, GBM stem cells (GSC), has been implicated in this recurrence. The chemotherapeutic agent etoposide is generally reserved for treating recurrent tumors; however, its effectiveness limited due to acute cumulative toxicities normal tissues. We investigate a novel combinatorial approach low-dose with an oncolytic HSV enhance antitumor activity limit drug toxicity. Experimental Design: In vitro , human cell lines GSCs were treated alone, herpes simplex virus (oHSV) G47Δ or the combination. Cytotoxic interactions analyzed using Chou–Talalay method, changes caspase-dependent apoptosis cycle determined. vivo most etoposide-resistant GSC, BT74, was implanted intracranially either treatment alone Analysis included effects on survival, therapy-associated adverse events, histologic detection apoptosis. Results: varied their sensitivity by over 50-fold whereas similar. Combining moderately synergistic lines. This combination did not replication, but significantly increased single extended survival mice-bearing etoposide–insensitive intracranial GSC–derived tumors. Conclusions: increases tumors without side effects. These results establish as promising strategy treat resistant GBM. Clin Cancer Res; 17(23); 7383–93. ©2011 AACR .