Gene expression profiling showed downregulation of both Ras and CDK4/6 signaling pathway genes in MM-cells after ERK1/2i + CDK4/6i at concentration ratios of 3:1 or 2:1, which are associated with synergistic cytotoxicity (Figs. 4A, S3, 2B, C). This evidence concerns the gene MAPK3 and Miyoshi myopathy.