{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Malone CF"],"funding":["National Cancer Institute (NCI)","Friends For Life","National Cancer Institute","NCI NIH HHS","The Pussycat Foundation"],"pagination":["285-300"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9938728"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["83(2)"],"pubmed_abstract":["Aberrant RAS/MAPK signaling is a common driver of oncogenesis that can be therapeutically targeted with clinically approved MEK inhibitors. Disease progression on single-agent MEK inhibitors is common, however, and combination therapies are typically required to achieve significant clinical benefit in advanced cancers. Here we focused on identifying MEK inhibitor-based combination therapies in neuroblastoma with mutations that activate the RAS/MAPK signaling pathway, which are rare at diagnosis but frequent in relapsed neuroblastoma. A genome-scale CRISPR-Cas9 functional genomic screen was deployed to identify genes that when knocked out sensitize RAS-mutant neuroblastoma to MEK inhibition. Loss of either CCNC or CDK8, two members of the mediator kinase module, sensitized neuroblastoma to "],"journal":["Cancer research"],"pubmed_title":["Transcriptional Antagonism by CDK8 Inhibition Improves Therapeutic Efficacy of MEK Inhibitors."],"pmcid":["PMC9938728"],"funding_grant_id":["P01 CA217959","F32 CA243266","1P01 CA217959","R35 CA210030"],"pubmed_authors":["Thayakumar A","Stegmaier K","Goodale A","Alexe G","Kim M","Engel K","Khalid D","Gray NS","Hatcher JM","Forman AB","Malone CF","Robichaud A","Conway AS","Meyer A","Piccioni F"],"additional_accession":[]},"is_claimable":false,"name":"Transcriptional Antagonism by CDK8 Inhibition Improves Therapeutic Efficacy of MEK Inhibitors.","description":"Aberrant RAS/MAPK signaling is a common driver of oncogenesis that can be therapeutically targeted with clinically approved MEK inhibitors. Disease progression on single-agent MEK inhibitors is common, however, and combination therapies are typically required to achieve significant clinical benefit in advanced cancers. Here we focused on identifying MEK inhibitor-based combination therapies in neuroblastoma with mutations that activate the RAS/MAPK signaling pathway, which are rare at diagnosis but frequent in relapsed neuroblastoma. A genome-scale CRISPR-Cas9 functional genomic screen was deployed to identify genes that when knocked out sensitize RAS-mutant neuroblastoma to MEK inhibition. Loss of either CCNC or CDK8, two members of the mediator kinase module, sensitized neuroblastoma to ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-29T00:27:26.278Z","creation":"2025-04-06T16:24:19.954Z"},"accession":"S-EPMC9938728","cross_references":{"pubmed":["36398965"],"doi":["10.1158/0008-5472.CAN-21-4309","10.1158/0008-5472.can-21-4309"]}}