Based on the above findings, it can be hypothesized that detection of high TGF-β1 plasma level, SMAD4SNP rs113545983 or high TGF-βR2/SMAD4 tumor protein expression ratio may suggest a dependence on this pathway in patients with advanced pancreatic cancer and this subset may potentially benefit from TGF-β-targeted therapy. Here, SMAD4 is linked to familial pancreatic carcinoma.