Abemaciclib, a selective cdk4/6 inhibitor, restricts the growth of pediatric ependymomas

Muh Lii Liang, Chun-Han Chen, Yun Ru Liu, Man Hsu Huang, Yu Chen Lin, Tai Tong Wong, Sey En Lin, Shing Shiung Chu, Yi Huei Ding, Tsung-Han Hsieh

研究成果: 雜誌貢獻文章同行評審

摘要

Pediatric ependymomas are a type of malignant brain tumor that occurs in children. The overall 10-year survival rate has been reported as being 45–75%. Maximal safe surgical resection combined with adjuvant chemoradiation therapy is associated with the highest overall and progression-free survival rates. Despite aggressive treatment, one-third of ependymomas exhibit recurrence within 2 years of initial treatment. Therefore, this study aimed to find new agents to overcome chemoresistance and defer radiotherapy treatment since, in addition, radiation exposure may cause long-term side effects in the developing brains of young children. By using integrated bioinformatics and through experimental validation, we found that at least one of the genes CCND1 and CDK4 is overexpressed in ependymomas. The use of abemaciclib, a highly selective CDK4/6 inhibitor, effectively inhibited cell proliferation and reduced the expression of cell-cycle-related and DNA-repair-related gene expression via the suppression of RB phosphorylation, which was determined through RNA-seq and Western blot analyses. Furthermore, abemaciclib effectively induced cell death in vitro. The efficiency of abemaciclib was validated in vivo using subcutaneously implanted ependymoma tissues from patient-derived xenografts (PDXs) in mouse models. Treatment with abemaciclib showed encouraging results in preclinical pediatric ependymoma models and represents a potential therapeutic strategy for treating challenging tumors in children.

原文英語
文章編號3597
頁(從 - 到)1-17
頁數17
期刊Cancers
12
發行號12
DOIs
出版狀態已發佈 - 十二月 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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