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

BMC Cancer
Shutaro YamadaNorifumi Naka

Abstract

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 of phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs. Here we aimed to investigate the therapeutic potential of TAS-115 against SS. We first evaluated which signalling pathway was relevant to the viability of three human SS cell lines: Yamato-SS, SYO-1 and HS-SY-II. Next, we assessed the anticancer activity and mechanism of action of TAS-115 in these SS cell lines. Finally, we compared the ability of TAS-115 to inhibit c-MET and PDGFRα phosphorylation with that of pazopanib. We classified the SS cell lines as c-MET-dependent or PDGFRα-dependent based upon the differences in the signalling pathway relevant for growth and/or survival. We also found that c-MET and PDGFRα were the primary activators of both phosphatidylinositol 3-kinase/AKT and mitogen-activated protein kinase pathways in c-MET-dependent and PDGFRα-dependent SS cells, respect...Continue Reading

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Citations

Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Alberto PucciniFrancesca Battaglin
Dec 13, 2018·American Journal of Respiratory Cell and Molecular Biology·Kazuya KoyamaYasuhiko Nishioka
Dec 13, 2018·American Journal of Respiratory Cell and Molecular Biology·Carole L Wilson, Chi F Hung

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Methods Mentioned

BETA
xenograft
xenografts

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