TAS‐115 inhibits PDGFRα/AXL/FLT‐3 signaling and suppresses lung metastasis of osteosarcoma

Osteosarcoma is the most common malignant bone tumor in adolescence and childhood. Metastatic osteosarcoma has a poor prognosis with an overall 5‐year survival rate of approximately 20%. TAS‐115 is a novel multiple receptor tyrosine kinase inhibitor that is currently undergoing clinical trials. Using the mouse highly lung‐metastatic osteosarcoma cell line, LM8, we showed that TAS‐115 suppressed the growth of subcutaneous grafted tumor and lung metastasis of osteosarcoma at least partially through the inhibition of platelet‐derived growth factor receptor alpha, AXL, and Fms‐like tyrosine kinase 3 phosphorylation. We also show that these signaling pathways are activated in various human osteosarcoma cell lines and are involved in proliferation. Our results suggest that TAS‐115 may have potential for development into a novel treatment for metastatic osteosarcoma. TAS‐115 suppressed the growth of subcutaneous grafted tumor and lung metastasis of a mouse spontaneous highly metastatic osteosarcoma (OS) cell line, LM8. TAS‐115 exerts antitumor effects against OS cell lines partially via the inhibition of PDGFRα, AXL, and FLT‐3 signaling. TAS‐115 may be a potential novel therapeutic agent for patients with metastatic OS.