Based on preclinical studies suggesting that up-regulation of the PI3K-AKT-mTOR signaling pathway causes acquired resistance to CDK4/6 inhibitors, the mTOR inhibitor everolimus and PI3K inhibitor alpelisib have been clinically used to manage CDK4/6 inhibitor-resistant breast cancer [1, 13]. The gene discussed is AKT1; the disease is breast cancer.