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. This evidence concerns the gene SMAD3 and esophageal squamous cell carcinoma.