It was suggested that Smad3-P27/P21-cyclin E1/CDK2-phosphorylated retinoblastoma protein pathways might be involved in IGFBP-3-mediated radiosensitivity transition in esophageal squamous cell carcinoma (ESCC) the most prevalent histologic type of esophageal cancer in China and eastern countries. The gene discussed is SMAD3; the disease is esophageal cancer.