CDK4 and neoplasm: Combinations with MEK inhibitors are more likely to prevent the appearance of resistance to CDK4/6is and generate a senescence response in tumor cells, partly because they oppose the increased levels of cyclins D that are most often observed in response to CDK4/6is (due to stabilization inside CDK4/6 complexes, but also to increased AP1 (activator protein 1) transcriptional activity [102,103,104,105,106]).