{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Zhang S"],"funding":["NICHD NIH HHS","NCI NIH HHS"],"pubmed_abstract":["Alveolar rhabdomyosarcoma (aRMS) is a fusion-driven pediatric cancer with poor survival and limited therapeutic options. To uncover novel vulnerabilities, we employed complex-based analysis of the DepMap functional genomic data, identifying CDK8 as a dependency in aRMS. Both <i>CDK8</i> knockout and pharmacologic inhibition impaired tumor cell growth and induced myogenic differentiation <i>in vitro</i> and <i>in vivo</i>. Compared to genetic loss, CDK8 inhibition induced more dynamic transcriptional changes. With a genome-scale CRISPR-Cas9 drug modifier screen, we determined that the maximal anti-tumor activity of the CDK8 inhibitor requires the presence of the Mediator kinase module and transcriptional cooperation with the SAGA complex. We further identified SIX4 as a key transcription fa"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.07.14.663986"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12338617"],"repository":["biostudies-literature"],"pubmed_title":["CDK8 Inhibition Releases the Muscle Differentiation Block in Fusion-driven Alveolar Rhabdomyosarcoma."],"pmcid":["PMC12338617"],"funding_grant_id":["U54 CA231630","R35 CA283977","T32 HD094671"],"pubmed_authors":["Rees M","Roth J","Alexe G","Barbar L","Guedes B","Zhang S","Shern JF","Engel K","Just M","Ross K","Kovach A","Digiovanni G","Oristian KM","Counter CM","Stegmaier K","Cerda-Smith C","Zimmerman SP","Granum D","Linardic CM","Mendes E","Bentley R","Le Roux O","Wood KC","Malone CF","Fahs A"],"additional_accession":[]},"is_claimable":false,"name":"CDK8 Inhibition Releases the Muscle Differentiation Block in Fusion-driven Alveolar Rhabdomyosarcoma.","description":"Alveolar rhabdomyosarcoma (aRMS) is a fusion-driven pediatric cancer with poor survival and limited therapeutic options. To uncover novel vulnerabilities, we employed complex-based analysis of the DepMap functional genomic data, identifying CDK8 as a dependency in aRMS. Both <i>CDK8</i> knockout and pharmacologic inhibition impaired tumor cell growth and induced myogenic differentiation <i>in vitro</i> and <i>in vivo</i>. Compared to genetic loss, CDK8 inhibition induced more dynamic transcriptional changes. With a genome-scale CRISPR-Cas9 drug modifier screen, we determined that the maximal anti-tumor activity of the CDK8 inhibitor requires the presence of the Mediator kinase module and transcriptional cooperation with the SAGA complex. We further identified SIX4 as a key transcription fa","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-04-08T15:50:16.603Z","creation":"2026-04-08T05:37:07.754Z"},"accession":"S-EPMC12338617","cross_references":{"pubmed":["40791356"],"doi":["10.1101/2025.07.14.663986"]}}