Exploration of signaling pathways, both of the TGF-beta dependent and of the crosstalk with CD36 and CD97, or with other intracellular signaling molecules, offers potential hints for identification and stratification of pancreatic cancer cell subtypes, cell cooperation in tumor microenvironment, and optimization of therapies, based on particular aspects of each subset. This evidence concerns the gene ADGRE2 and familial pancreatic carcinoma.