AKT1 and breast carcinoma: 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.