biostudies-literatureHormann ANCI NIH HHS28625-28637https://www.ebi.ac.uk/biostudies/studies/S-EPMC6033344biostudies-literatureUnknown9(47)Genotype specific vulnerabilities of cancer cells constitute a promising strategy for the development of new therapeutics. Deletions of non-essential genes in tumors can generate unique vulnerabilities which could be exploited therapeutically. The <i>MTAP</i> gene is recurrently deleted in human cancers because of its chromosomal proximity to the tumor suppressor gene <i>CDKN2A</i>. Recent studies have uncovered an increased dependency of <i>MTAP</i>-deleted cancer cells on the function of a PRMT5 containing complex, including WDR77, PRMT5 and the kinase RIOK1. As RIOK1 kinase activity constitutes a potential therapeutic target, we wanted to test if <i>MTAP</i> deletion confers increased sensitivity to RIOK1 inhibition. Using CRISPR/Cas9-mediated genome engineering we generated analog sensOncotargetRIOK1 kinase activity is required for cell survival irrespective of <i>MTAP</i> status.PMC6033344P01 CA013106R01 CA174793Ehrenhofer KKrammer TWohrle SHopfgartner BSchweifer NReiser CBader GCorcokovic MKocher TKraut NHormann APetronczki MNeumuller RAVakoc CRShi JPearson MfalseRIOK1 kinase activity is required for cell survival irrespective of <i>MTAP</i> status.Genotype specific vulnerabilities of cancer cells constitute a promising strategy for the development of new therapeutics. Deletions of non-essential genes in tumors can generate unique vulnerabilities which could be exploited therapeutically. The <i>MTAP</i> gene is recurrently deleted in human cancers because of its chromosomal proximity to the tumor suppressor gene <i>CDKN2A</i>. Recent studies have uncovered an increased dependency of <i>MTAP</i>-deleted cancer cells on the function of a PRMT5 containing complex, including WDR77, PRMT5 and the kinase RIOK1. As RIOK1 kinase activity constitutes a potential therapeutic target, we wanted to test if <i>MTAP</i> deletion confers increased sensitivity to RIOK1 inhibition. Using CRISPR/Cas9-mediated genome engineering we generated analog sens2018-01-01T00:00:00Z2018 Jun2025-04-25T21:18:46.396Z2019-03-26T23:45:58ZS-EPMC60333442998388510.18632/oncotarget.25586