Esophageal squamous cell carcinoma (ESCC) is a very aggressive cancer, and the ΔNp63α/RSK4/GSK-3β axis (RSK4: ribosomal protein S6 kinase A6; GSK: glycogen synthase kinase 3β) plays a pivotal role in radioresistance in ESCC. The gene discussed is GSK3B; the disease is esophageal squamous cell carcinoma.