biostudies-literatureKazi ANCIJoseph &amp; Ann Matella Fund for Pancreatic Cancer ResearchNCI NIH HHSNIHH. Lee Moffitt Cancer Center &amp; Research Institute4012-4024https://www.ebi.ac.uk/biostudies/studies/S-EPMC8493485biostudies-literatureUnknown27(14)<h4>Purpose</h4>Among human cancers that harbor mutant (mt) KRas, some, but not all, are dependent on mt KRas. However, little is known about what drives KRas dependency.<h4>Experimental design</h4>Global phosphoproteomics, screening of a chemical library of FDA drugs, and genome-wide CRISPR/Cas9 viability database analysis were used to identify vulnerabilities of KRas dependency.<h4>Results</h4>Global phosphoproteomics revealed that KRas dependency is driven by a cyclin-dependent kinase (CDK) network. CRISPR/Cas9 viability database analysis revealed that, in mt KRas-driven pancreatic cancer cells, knocking out the cell-cycle regulators CDK1 or CDK2 or the transcriptional regulators CDK7 or CDK9 was as effective as knocking out KRas. Furthermore, screening of a library of FDA drugs identifClinical cancer research : an official journal of the American Association for Cancer ResearchGlobal Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer.PMC8493485R01 CA242003U54 CA233444R35 CA197731P30 CA076292Yang HUnderwood PWelsh EATrevino JChen LXiang SFang BKazi AKoomen JSebti SMWilliams TMVangipurapu RHusain KMalafa MBeato FFleming JBfalseGlobal Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer.<h4>Purpose</h4>Among human cancers that harbor mutant (mt) KRas, some, but not all, are dependent on mt KRas. However, little is known about what drives KRas dependency.<h4>Experimental design</h4>Global phosphoproteomics, screening of a chemical library of FDA drugs, and genome-wide CRISPR/Cas9 viability database analysis were used to identify vulnerabilities of KRas dependency.<h4>Results</h4>Global phosphoproteomics revealed that KRas dependency is driven by a cyclin-dependent kinase (CDK) network. CRISPR/Cas9 viability database analysis revealed that, in mt KRas-driven pancreatic cancer cells, knocking out the cell-cycle regulators CDK1 or CDK2 or the transcriptional regulators CDK7 or CDK9 was as effective as knocking out KRas. Furthermore, screening of a library of FDA drugs identif2021-01-01T00:00:00Z2021 Jul2025-04-04T02:04:09.174Z2022-02-11T15:16:02.3ZS-EPMC84934853387945910.1158/1078-0432.ccr-20-478110.1158/1078-0432.CCR-20-4781