For instance, a robust increase in the cellcycle inhibitor, p21, is observed with the application of many HDACi.38 However, p21 is the tip of the iceberg withmany thousands of genes being both up- and downregulated by HDAC inhibition.Furthermore, many cancer cells have a deregulated G1/S transitionat which inhibition DEP domain-containing mTOR interacting protein(DEPTOR) of cyclin D/CDK4/6 is unlikely to be a major factor. This evidence concerns the gene CDK4 and cancer.