{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kazi A"],"funding":["NCI","Joseph &amp; Ann Matella Fund for Pancreatic Cancer Research","NCI NIH HHS","NIH","H. Lee Moffitt Cancer Center &amp; Research Institute"],"pagination":["4012-4024"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8493485"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(14)"],"pubmed_abstract":["<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 identif"],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pubmed_title":["Global Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer."],"pmcid":["PMC8493485"],"funding_grant_id":["R01 CA242003","U54 CA233444","R35 CA197731","P30 CA076292"],"pubmed_authors":["Yang H","Underwood P","Welsh EA","Trevino J","Chen L","Xiang S","Fang B","Kazi A","Koomen J","Sebti SM","Williams TM","Vangipurapu R","Husain K","Malafa M","Beato F","Fleming JB"],"additional_accession":[]},"is_claimable":false,"name":"Global Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer.","description":"<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 identif","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jul","modification":"2025-04-04T02:04:09.174Z","creation":"2022-02-11T15:16:02.3Z"},"accession":"S-EPMC8493485","cross_references":{"pubmed":["33879459"],"doi":["10.1158/1078-0432.ccr-20-4781","10.1158/1078-0432.CCR-20-4781"]}}