CCND1 and esophageal adenocarcinoma: For esophageal adenocarcinoma, metformin has been shown to block cell cycle of G0 to G1 transition in the cell cycle, accompanied by decreased cyclin D1 levels and retinoblastoma protein phosphorylation, as well as reduced phosphorylation of the epidermal growth factor receptor, insulin-like growth factor, and angiogenesis-related proteins (33).