Potential therapeutic efficiency of pan-ERBB inhibitors for canine glioma

Abstract

Canine glioma is one of the most common brain tumors and has a poor prognosis. Therefore, an effective chemotherapy is desired. A previous study has indicated that the signaling involving one of the epidermal growth factor receptor (EGFR), ERBB4 is a promising therapeutic target. In the current study, the anti-tumor effects of pan-ERBB inhibitors that can inhibit phosphorylation of ERBB4 were evaluated in a canine glioblastoma cell line in vitro and in vivo. As a result, both afatinib and dacomitinib successfully decreased the expression of phosphorylated ERBB4 and signi cantly decreased the number of viable cells. Furthermore, both reagents prolonged the survival time of orthotopic xenografted mice. With regard to the downstream molecules of ERBB4, afatinib suppressed the expression of phosphorylated Akt and phosphorylated Extracellular signal-related kinases1 and 2 (ERK1/2) and, in addition, induced apoptotic cell death. Thus, pan-ERBB inhibition was considered a potential promising therapeutic strategy for canine glioma.