Therapeutic potential of TAS-115 via c-MET and PDGFRα signal inhibition for synovial sarcoma

摘要: The prognosis of synovial sarcoma (SS), an aggressive soft tissue sarcoma, remains poor. We previously reported that c-MET or platelet-derived growth factor receptor α (PDGFRα) signalling pathway is related to SS progression based upon the findings phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 a novel c-MET/ vascular endothelial receptor-targeting inhibitor has been shown inhibit multiple RTKs. Here we aimed investigate therapeutic potential against SS. first evaluated which was relevant viability three human cell lines: Yamato-SS, SYO-1 and HS-SY-II. Next, assessed anticancer activity mechanism action in these lines. Finally, compared ability PDGFRα phosphorylation with pazopanib. classified lines as c-MET-dependent PDGFRα-dependent differences for and/or survival. also found were primary activators both phosphatidylinositol 3-kinase/AKT mitogen-activated protein pathways cells, respectively. treatment blocked well their downstream effectors, leading marked inhibition types vitro vivo studies. Furthermore, phosphorylation, on at least four representative autophosphorylation sites, impeded by equivalently These experimental results have demonstrated significance survival tumours. monotherapy may benefit patients whose tumours are dependent either functioning suppress pathways.