SMAD4 and colorectal cancer: In many studies that have been conducted in the past 20 years it was found that the loss of SMAD4 function alone does not initiate a tumor, but it may promote the progression of tumors which have been initiated by other molecular defects, like the activation of KRas activation in the case of pancreatic duct adenocarcinoma and the inactivation of APC in colorectal cancer (20, 24).