During the later part of the disease, other genetic and epigenetic alterations occur in EGFR, HER2, p16Ink4a, p53, Smad/DPC4, and other genes (Aguirre et al, 2003; Hezel et al, 2006) that facilitate the development of pancreatic adenocarcinoma and, subsequently, its metastasis (Aguirre et al, 2003; Hingorani et al, 2005; Bardeesy et al, 2006; Hezel et al, 2006). Here, SMAD4 is linked to pancreatic adenocarcinoma.