Researchers also found the resistance to rapamycin in ESCC patients, the reason is that rapamycin induced a large number of negative feedback loops from p70S6K to PI3K or mTORC2, which significantly activated the PI3K/Akt signaling pathway and weakened the anticancer effect of rapamycin (71, 75). This evidence concerns the gene AKT1 and esophageal squamous cell carcinoma.