A clinical consequence of the frequent functional loss of TRAIL-receptors in pancreatic cancer may be represented by the fact that many pancreatic tumors do not respond to the administration of the specific agonistic antibodies targeting either TRAIL-R1 such as Mapatumumab or TRAIL-R2 such as Tigatuzumab [27]. Here, TNFRSF10B is linked to familial pancreatic carcinoma.