Thus, Goel and coworkers have developed a transgenic model of HER2-positive breast cancer (MMTV-HER2) and they have used the tumor cells that originated in these transgenic mice to show that cyclin D1/cyclin-dependent kinase 4 (CDK4) mediated resistance to HER2-targeted therapy and that CDK4/6 inhibitors delayed a HER2-positive tumor relapse [433]. Here, CDK4 is linked to breast carcinoma.