https://scholars.lib.ntu.edu.tw/handle/123456789/469965
標題: | Therapeutic targeting of non-oncogene dependencies in high-risk neuroblastoma | 作者: | Huang, C.-T. Hsieh, C.-H. Lee, W.-C. Liu, Y.-L. Yang, T.-S. WEN-MING HSU Oyang, Yen-Jen Huang, H.-C. HSUEH-FEN JUAN |
公開日期: | 2019 | 出版社: | American Association for Cancer Research Inc. | 卷: | 25 | 期: | 13 | 起(迄)頁: | 4063-4078 | 來源出版物: | Clinical Cancer Research | 摘要: | Purpose: Neuroblastoma is a pediatric malignancy of the sympathetic nervous system with diverse clinical behaviors. Genomic amplification ofMYCNoncogene 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. ? 2019 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068322545&doi=10.1158%2f1078-0432.CCR-18-4117&partnerID=40&md5=34b7253821abc92d6ea5d01716c2fb6c https://scholars.lib.ntu.edu.tw/handle/123456789/469965 |
ISSN: | 1078-0432 | DOI: | 10.1158/1078-0432.CCR-18-4117 | SDG/關鍵字: | dactolisib; niclosamide; nucleoside diphosphate kinase; pyrvinium embonate; vinblastine; vincristine; antineoplastic agent; N Myc proto oncogene protein; transcriptome; tumor marker; animal experiment; animal model; antineoplastic activity; Article; cancer prognosis; controlled study; down regulation; drug approval; drug efficacy; drug potentiation; drug targeting; event free survival; Food and Drug Administration; gene expression; high risk patient; human; human cell; in vitro study; in vivo study; male; mouse; neuroblastoma; nonhuman; oncogene c myb; overall survival; prediction; priority journal; proteomics; quantitative analysis; recurrence free survival; cell cycle; drug development; gene amplification; gene expression profiling; gene expression regulation; genetics; liquid chromatography; molecularly targeted therapy; mortality; neuroblastoma; pathology; procedures; tandem mass spectrometry; tumor cell line; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cell Cycle; Cell Line, Tumor; Chromatography, Liquid; Drug Discovery; Gene Amplification; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; N-Myc Proto-Oncogene Protein; Neuroblastoma; Proteomics; Tandem Mass Spectrometry; Transcriptome |
顯示於: | 醫學系 |
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