Given that the aberrant activation of Src/Akt/β-catenin and the upregulation of Bcl-2 were considered to be involved in NHE9-induced CRT resistance in ESCC, we attempted to weaken the resistance by applying the relevant targeted inhibitors to decrease the activation of Src and Bcl-2. The gene discussed is AKT1; the disease is esophageal squamous cell carcinoma.