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Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness and drug resistance. Only a small fraction of GB patients survives longer than 24\u2009months from the time of diagnosis (ie, long\u2010term survivors [LTS]). In our study, we aimed to identify molecular markers associated with favorable GB prognosis as a basis to develop therapeutic applications to improve patients' outcome. We have recently assembled a proteogenomic dataset of 87\u2009GB clinical samples of varying survival rates. Following RNA\u2010seq and mass spectrometry (MS)\u2010based proteomics analysis, we identified several differentially expressed genes and proteins, including some known cancer\u2010related pathways and some less established that showed higher expression in short\u2010term (&lt;6\u2009months) survivors (STS) compared to LTS. One such target found was deoxyhypusine hydroxylase (DOHH), which is known to be involved in the biosynthesis of hypusine, an unusual amino acid essential for the function of the eukaryotic translation initiation factor 5A (eIF5A), which promotes tumor growth. We consequently validated DOHH overexpression in STS samples by quantitative polymerase chain reaction (qPCR) and immunohistochemistry. We further showed robust inhibition of proliferation, migration and invasion of GB cells following silencing of DOHH with short hairpin RNA (shRNA) or inhibition of its activity with small molecules, ciclopirox and deferiprone. Moreover, DOHH silencing led to significant inhibition of tumor progression and prolonged survival in GB mouse models. Searching for a potential mechanism by which DOHH promotes tumor aggressiveness, we found that it supports the transition of GB cells to a more invasive phenotype via epithelial\u2010mesenchymal transition (EMT)\u2010related pathways.<\/jats:p>","DOI":"10.1002\/ijc.34545","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T18:35:36Z","timestamp":1683225336000},"page":"654-668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Deoxyhypusine hydroxylase: A novel therapeutic target differentially expressed in short\u2010term vs long\u2010term survivors of glioblastoma"],"prefix":"10.1002","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-1107","authenticated-orcid":false,"given":"Paula","family":"Ofek","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Sackler Faculty of Medicine Tel Aviv University  Tel Aviv 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