CDK4 and breast cancer: In the clinical use of cyclin D-CDK4 inhibitor (CDK4I) in HR+ breast cancer, the problem of CDK4 inhibitor resistance is usually caused by compensatory CDK2 activity.309 A therapeutic liposome peptide NP-ALT inhibits the tyrosine phosphorylation of p27kip1 (CDKN1B) and the activity of CDK4 and CDK2 by inducing ROS and RIPK1 dependent necroptosis in breast cancer cells and xenotransplantation models resistant to endocrine therapy.