Trabectedin is a promising antitumour agent for synovial sarcoma

Abstract

Synovial sarcoma (SS) is an aggressive soft tissue tumour with poor prognosis. Using five human SS cell lines, we examined the cytotoxic effects of trabectedin (ET-743; Yondelis^®), a novel marine natural product, which was approved in Europe for the treatment of soft tissue sarcomas (STS). The significant growth inhibitory effects were observed in all SS cell lines below nanomolar concentration of trabectedin. Furthermore, trabectedin significantly suppressed the tumour growth in xenograft models. Flow cytometer analysis in vitro and immunohistochemical analysis in vivo revealed its effect of cell cycle inhibition and apoptosis induction. We also examined the expression of ERCC1, 5 and BRCA1 in SS cell lines and clinical samples, and majority of them showed highly trabectedin-sensitive pattern as previously reported in other cancers. Our preclinical data indicated that trabectedin could be a promising therapeutic option for patients with SS.

Keywords:

• Synovial sarcoma
• Trabectedin
• ERCC1
• ERCC5
• BRCA1

Acknowledgements

We wish to thank Dr. Toshifumi Ozaki for providing a SS cell line, SYO-1. We thank Mari Shinkawa and Asa Tada for their technical support.

Conflict of interest

There are no potential conflicts of interest to declare

Funding

This work was supported by the Osaka Nanbyou Zaidan and the Japan Society for the Promotion of Science, JSPS KAKENHI [grant number 24592233], [grant number 26462264]; Practical Research for Innovative Cancer Control from Japan Agency For Medical Research and development, AMED.