CDK4 and cancer: Finally, the novel positive feedback pathways identified here from CDK4 and CDK2 to facilitate CDK4 activation may explain the relative resistance to receptor or cell signaling kinase inhibitory drugs of cancer cells that have intrinsically strong CDK4 activity (e.g. due to frequent CDKN2A deletion or Cdk4 amplification) and/or CDK2 activity (e.g. due to deregulation of cyclin E).