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Potential therapeutic efficiency of pan-ERBB inhibitors for canine glioma
Shunsuke Noguchi1, Moeka Yasumura2
1Laboratory of Veterinary Radiology, Graduate School of Veterinary Science, Osaka Metropolitan University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka, 598-8531, Japan. snoguchi@omu.ac.jp.
Abstract:
Canine glioma is one of the most common brain tumors with poor prognosis, making effective chemotherapy highly desirable. Previous studies have suggested that ERBB4, a signaling molecule involving one of the epidermal growth factor receptors (EGFR), may be a promising therapeutic target. In this study, the anti-tumor effects of pan-ERBB inhibitors, which can inhibit the phosphorylation of ERBB4, were evaluated both in vitro and in vivo using a canine glioblastoma cell line. The results demonstrated that both afatinib and dacomitinib effectively reduced the expression of phosphorylated ERBB4, and significantly decreased the number of viable cells, ultimately prolonging the survival time of orthotopically xenografted mice. Further downstream of ERBB4, afatinib was found to suppress the expression of phosphorylated Akt and phosphorylated Extracellular signal-related kinases1 and 2 (ERK1/2) and induced apoptotic cell death. Thus, pan-ERBB inhibition is a promising therapeutic strategy for the treatment of canine gliomas.
Insights
Pan-ERBB inhibitors like afatinib and dacomitinib show promise for treating canine gliomas. These drugs target ERBB4, reducing tumor cell viability and extending survival in mice with brain tumors.
Area of Science:
- Oncology
- Veterinary Medicine
- Molecular Biology
Background:
- Canine glioma is a common brain tumor with a poor prognosis.
- ERBB4 (a member of the epidermal growth factor receptor family) is a potential therapeutic target.
Purpose of the Study:
- To evaluate the anti-tumor effects of pan-ERBB inhibitors on canine glioblastoma.
- To investigate the efficacy of afatinib and dacomitinib in preclinical models.
Main Methods:
- In vitro and in vivo studies using a canine glioblastoma cell line.
- Assessment of ERBB4 phosphorylation, cell viability, and tumor progression.
- Analysis of downstream signaling pathways (Akt, ERK1/2) and apoptosis induction.
Main Results:
- Afatinib and dacomitinib reduced phosphorylated ERBB4 expression.
- Both drugs significantly decreased canine glioblastoma cell viability.
- Treatment prolonged survival in mice with orthotopically xenografted tumors.
- Afatinib suppressed phosphorylated Akt and ERK1/2, inducing apoptosis.
Conclusions:
- Pan-ERBB inhibition is a viable therapeutic strategy for canine gliomas.
- Targeting ERBB4 offers a promising avenue for novel canine cancer treatments.
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