Based on the sustained activation of the Notch signaling pathway in pancreatic cancer and their key role in tumorigenesis and pancreatic cancer stem cell maintenance, we hypothesized that an adenovirus engineered with a chimeric sequence comprising Notch-responsive elements combined with the uPAR promoter might improve the transcription of E1A in neoplastic and cancer stem cells, thus enhancing viral tumor activity and oncoselectivity. Here, DHTKD1 is linked to familial pancreatic carcinoma.