CDK8 was initially identified as an oncogenerequired for β-catenin-inducedtranscription in colorectal cancer and later implicated in regulatingthe AP1 family of transcription factors downstream of RAS/RAF/MEKsignaling.,,, Consistent with these roles in colorectalcancer, GSEA confirmed CDK8’s role in oncogenic pathways, showinginhibition of β-catenin/TCF, KRAS/MAPK, and ATF target genesfollowing inhibitor treatment or loss of both Mediator kinases incolorectal cancer cells dependent on oncogenic beta-catenin and KRAS/BRAFsignaling. The gene discussed is HNF4A; the disease is colorectal cancer.