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Supplementary Table S10 from Therapeutic Targeting of Non-oncogene Dependencies in High-risk Neuroblastoma

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posted on 2023-03-31, 21:04 authored by 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

Supplementary Table S10

Funding

Ministry of Science and Technology

NHRI

History

ARTICLE ABSTRACT

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. By using a gene expression–based integrative approach, we identified prognostic signatures and potentially effective single agents and drug combinations for high-risk neuroblastoma. 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. Our results establish a gene expression–based strategy to interrogate cancer biology and inform drug discovery and repositioning for high-risk neuroblastoma.