SMAD4 and neoplasm: Disruption of signalling, primarily through SMAD4 loss, is detected in roughly 50% of PDAC cases, and the tumour suppressive activity of the pathway has been demonstrated in mouse models of PDAC, with deletion of SMAD4 alongside oncogenic Kras accelerating PDAC progression, often via the development of intraductal papillary mucinous neoplasia (IPMN) [14,17,18].