Interestingly, the increased amount of free TGF-β, which is suspected to be associated with a higher risk of pancreatic cancer [24] and resistance to anticancer treatment [25], resulted from the inability to trigger activation of the Smad dependent pathway (primarily due to downregulation of Smad4) and to induce expression of the Smad4 target and TGF-β inhibitor biglycan. This evidence concerns the gene SMAD4 and pancreatic neoplasm.