Long-term CDK4i treatment, commonly used for luminal A breast cancer, activates alternative pathways, such as PI3K/AKT/mTOR, androgen receptor, and Hippo signaling (12, 13, 15, 16), along with transcriptional reprogramming via noncoding RNAs (14, 58), promoting the development of drug resistance. This evidence concerns the gene AKT1 and breast cancer.