MYC and neoplasm: Our RNAseq analysis revealed that compared to either single agent, LXH254 plus trametinib significantly (FDR < 0.01) downregulated the well-established and potential oncogenic events including cell proliferation (Myc targets), cell cycle (E2F targets and G2M checkpoint), DNA repair as well as energy metabolism oxidative phosphorylation, and significantly (FDR < 0.01) upregulated the tumor-suppressing events― interferon alpha and gamma response― all of which may contribute to mechanisms of sensitivity to this combinatorial approach.