BoneKEy Reports | BoneKEy Watch
ErbB3 emerges as an exciting therapeutic target in osteosarcoma
Osteosarcoma treatment often fails because of the development of chemoresistance. Jullien et al. explored the role of ErbB3, one member of the erythroblastic leukemia oncogene homolog family, demonstrating that cultured human osteosarcoma cell lines express ErbB3 in large quanities.
When they examined osteosarcoma samples from patients with different grades of disease, the authors also found that ErbB3 expression was greater in primary bone tumors than in unaffected osteoblasts. Levels of expression increased in recurrent and metastatic tumors, and so correlated with tumor grade.
Experiments in vitro and in vivo in a mouse allograft model suggested that silencing ErbB3 could have potentially beneficial effects. Cultured cells treated with specifically designed short hairpin RNA to block expression of ErbB3 showed both lower rates of cell replication and decreased migration, and lost the capacity to be invasive. In mice, silencing ErbB3 led to a decrease in cell proliferation in the tumor (25% lower than controls), slowing tumor growth significantly.
Editor’s comment: This study presents strong evidence that ErbB3 acts as a key factor that determines osteosarcoma progression. Silencing ErbB3 therefore emerges as a promising therapeutic strategy and may circumvent the chemoresistance observed in many osteosarcomas.
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