Synergistic treatment involving the TGF-β receptor I (TGFβRI) kinase inhibitor (vactosertib, or EW-7197) can increase the antitumor activity of gemcitabine against pancreatic cancer cells compared to gemcitabine treatment alone and inhibit TGF-β/Smad2 signaling pathway to decrease the production of extracellular matrix (ECM) proteins such as collagens, fibronectin, and alpha-smooth muscle actin (α-SMA) [118]. This evidence concerns the gene ACTA1 and familial pancreatic carcinoma.