Therapeutic Targeting of Non-oncogene Dependencies in High-risk Neuroblastoma

Chen-Tsung Huang, Chiao-Hui Hsieh, Wen-Chi Lee, Yen-Lin Liu, Tsai-Shan Yang, Wen-Ming Hsu, Yen-Jen Oyang, Hsuan-Cheng Huang, Hsueh-Fen Juan

研究成果: 雜誌貢獻文章同行評審

5 引文 斯高帕斯(Scopus)

摘要

Purpose: Neuroblastoma is a pediatric malignancy of the sympathetic nervous system with diverse clinical behaviors. Genomic amplification of MYCN oncogene has been shown to drive neuroblastoma pathogenesis and correlate with aggressive disease, but the survival rates for those high-risk tumors carrying no MYCN amplification remain equally dismal. The paucity of mutations and molecular heterogeneity has hindered the development of targeted therapies for most advanced neuroblastomas. We use an alternative method to identify potential drugs that target nononcogene dependencies in high-risk neuroblastoma.Experimental Design: By using a gene expression-based integrative approach, we identified prognostic signatures and potentially effective single agents and drug combinations for high-risk neuroblastoma.Results: Among these predictions, we validated in vitro efficacies of some investigational and marketed drugs, of which niclosamide, an anthelmintic drug approved by the FDA, was further investigated in vivo We also quantified the proteomic changes during niclosamide treatment to pinpoint nucleoside diphosphate kinase 3 (NME3) downregulation as a potential mechanism for its antitumor activity.Conclusions: Our results establish a gene expression-based strategy to interrogate cancer biology and inform drug discovery and repositioning for high-risk neuroblastoma.
原文英語
頁(從 - 到)4063-4078
頁數16
期刊Clinical cancer research : an official journal of the American Association for Cancer Research
25
發行號13
早期上線日期四月 5 2019
DOIs
出版狀態已發佈 - 2019

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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