Anti-relapse effect of trametinib on a local minimal residual disease neuroblastoma mouse model

Yuichi Togashi, Tomoko Tanaka, Masakazu Takemoto, Yuki Takeuchi, Mayumi Higashi, Shigehisa Fumino, Tatsuro Tajiri

研究成果: Contribution to journalArticle査読

1 被引用数 (Scopus)

抄録

Purpose: We reported the in vitro and in vivo anti-tumor effects of trametinib, an MEK inhibitor, on neuroblastoma. However, long-term trametinib administration for bulky tumors failed to prevent local relapse. In this study, we established a local minimal residual disease (L-MRD) model to develop an optimal clinical protocol. Methods: We prepared an L-MRD model by implanting neuroblastoma cells (SK-N-AS) into the renal capsule of nude mice with total tumorectomy or sham operation 14 days later. These mice received post-operative administration of trametinib or vehicle for eight weeks. Relapse was measured once weekly. Flow cytometry was performed with SK-N-AS cells treated by trametinib. Results: Tumorectomy+trametinib dramatically suppressed relapse, and all mice survived during trametinib administration, while other treatments failed to suppress relapse. The survival rates for other groups were 20% in sham+trametinib, 17% in tumorectomy+vehicle, and 0% in sham+vehicle. Relapse occurred in the tumorectomy+trametinib group after withdrawal of trametinib administration. Flow cytometry revealed G1 arrest in SK-N-AS cells treated with trametinib. Conclusion: These findings suggested that trametinib was able to suppress relapse from minimal residual tumor cells. Therefore, we propose that trametinib be administered as an option for maintenance therapy after surgical and chemotherapeutic treatments for neuroblastoma in future clinical protocols.

本文言語英語
ページ(範囲)1233-1239
ページ数7
ジャーナルJournal of Pediatric Surgery
56
7
DOI
出版ステータス出版済み - 7 2021
外部発表はい

All Science Journal Classification (ASJC) codes

  • 小児科学、周産期医学および子どもの健康
  • 外科

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