The Promising Role of TGF- β/SMAD4 in Pancreatic Cancer: The future targeted therapy

The transforming growth factor β (TGF-β) superfamily includes a group of structurally related cytokines that regulate a wide variety of biological processes.The diversity of its action depends on the dynamic tissue microenvironment, and interplays among the factors involving in the signaling pathway.Although its expression is tightly regulated in normal tissue, overexpression of TGF-β has been identified in multiple tumor types, including pancreatic adenocarcinoma.In pancreatic tumorigenesis, TGF-β acts initially as a tumor suppressor through phosphorylation and activation of SMAD4/DPC4 gene.Mutation of SMAD4/ DPC4 gene results in carcinogenesis and tumor progression in many cancers like lung, colon, and pancreatic cancer.SMAD4 mutation is now recognized in >50% of pancreatic ductal carcinomas.This review is to evaluate the diagnostic and prognostic value targeting the TGF-β/SMAD4 pathway in pancreatic ductal adenocarcinoma.