Treatment with MEKi significantly blunted tumor growth of CDK4i/6i-resistant ALM cells, and the combination of CDK4i/6i + MEKi resulted in the greatest antitumor activity and decrease in cell cycle proteins (pRb, cyclin D, PLK1, FOXM1) relative to what could be achieved by the single-agents alone (Fig. 4J, Supplementary Figure H, I, J). Here, RB1 is linked to neoplasm.