In keeping with the complementary effect of dual targeting CK1ε and CDK4/6 in vitro, addition of CK1ε kinase inhibitor D 4476 dramatically enhanced the efficacy of ribociclib on retarding 4T1 and MDA-MB-231 tumor growth in vivo (Fig. 7g, h, Supplementary Fig. 7e, f). This evidence concerns the gene CDK4 and neoplasm.