Gene amplifications, especially in the genes encoding cyclin D1, D2, E1, and CDK 4 and 6; and deletions in the CDK inhibitor 2A gene (CDKN2A), are the two main cell-cycle-related changes in cancer causing deregulations in the cell cycle checkpoints.693 These mutations may develop during RTK-inhibitor treatment and lead resistance.647 Resistance to HER2-inhibitors, for instance, may be caused by cell cycle aberrations. This evidence concerns the gene ERBB2 and cancer.