TAS-115 inhibits PDGFRα/AXL/FLT-3 signaling and suppresses lung metastasis of osteosarcoma.
Naohiro YasudaSatoshi TakenakaSho NakaiTakaaki NakaiShutaro YamadaYoshinori ImuraHidetatsu OutaniKenichiro HamadaHideki YoshikawaNorifumi NakaPublished in: FEBS open bio (2020)
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.
Keyphrases
- tyrosine kinase
- poor prognosis
- epidermal growth factor receptor
- growth factor
- small cell lung cancer
- squamous cell carcinoma
- signaling pathway
- clinical trial
- long non coding rna
- acute myeloid leukemia
- depressive symptoms
- randomized controlled trial
- epithelial mesenchymal transition
- risk assessment
- soft tissue
- protein kinase
- pi k akt
- binding protein
- childhood cancer
- open label
- phase iii
- bone loss