The role of CDK8/19 in non-genetically acquired antitumor drug resistance has been demonstrated by the ability of selective small-molecule CDK8/19 inhibitors (CDK8/19i) to sensitize tumor cells or to prevent the emergence of resistance to chemotherapeutics including inhibitors of EGFR, HER2 and MEK [39–42]. This evidence concerns the gene CDK8 and neoplasm.