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. The gene discussed is AR; the disease is breast carcinoma.