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ID 113620
Title Alternative
Association Between SLFN11 and Antitumor Activity of Trabectedin
Author
Iwasaki, Junya Taiho Pharmaceutical|Tokushima University
Komori, Toshiharu Taiho Pharmaceutical
Nakagawa, Fumio Taiho Pharmaceutical
Nagase, Hideki Taiho Pharmaceutical
Uchida, Junji Taiho Pharmaceutical
Matsuo, Kenichi Taiho Pharmaceutical
Keywords
DNA repair
anticancer drug
sarcoma
Schlafen11
trabectedin
Content Type
Journal Article
Description
Background/Aim: Trabectedin is a DNA-damaging agent and has been approved for the treatment of patients with advanced soft tissue sarcoma. Schlafen 11 (SLFN11) was identified as a dominant determinant of the response to DNA-damaging agents. The aim of the study was to clarify the association between SLFN11 expression and the antitumor activity of trabectedin. Materials and Methods: The antitumor activity of trabectedin was evaluated under different expression levels of SLFN11 regulated by RNA interference and CRISPR-Cas9 systems, and the combined antitumor activity of ataxia telangiectasia and Rad3-related protein kinase (ATR) inhibitor and trabectedin in sarcoma cell lines using in vitro a cell viability assay and in vivo xenograft models. Results: SLFN11-knockdown cell lines had a lower sensitivity to trabectedin, compared to parental cells. ATR inhibitor enhanced the antitumor activity of trabectedin in SLFN11-knockdown cells and in a SLFN11-knockout xenograft model. Conclusion: SLFN11 expression might be a key factor in the antitumor activity of trabectedin.
Journal Title
Anticancer Research
ISSN
02507005
17917530
NCID
AA10625860
AA12440673
Publisher
The International Institute of Anticancer Research
Volume
39
Issue
7
Start Page
3553
End Page
3563
Published Date
2019-07
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Bioscience and Bioindustry