KRASG12D and TP53R167H Cooperate to Induce Pancreatic Ductal Adenocarcinoma in Sus scrofa Pigs

Daniel R. Principe, Nana Haahr Overgaard, Alex J. Park, Andrew M. Diaz, Carolina Torres, Ronald McKinney, Matthew J. Dorman, Karla Castellanos, Regina Schwind, David W. Dawson, Ajay Rana, Ajay Maker, Hidayatullah G. Munshi, Lauretta A. Rund, Paul J. Grippo, Lawrence B. Schook

Research output: Contribution to journalArticlepeer-review


Although survival has improved in recent years, the prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poor. Despite substantial differences in anatomy, physiology, genetics, and metabolism, the overwhelming majority of preclinical testing relies on transgenic mice. Hence, while mice have allowed for tremendous advances in cancer biology, they have been a poor predictor of drug performance/toxicity in the clinic. Given the greater similarity of sus scrofa pigs to humans, we engineered transgenic sus scrofa expressing a LSL-KRASG12D-TP53R167H cassette. By applying Adeno-Cre to pancreatic duct cells in vitro, cells self-immortalized and established tumors in immunocompromised mice. When Adeno-Cre was administered to the main pancreatic duct in vivo, pigs developed extensive PDAC at the injection site hallmarked by excessive proliferation and desmoplastic stroma. This serves as the first large animal model of pancreatic carcinogenesis, and may allow for insight into new avenues of translational research not before possible in rodents.

Original languageEnglish (US)
Article number12548
JournalScientific reports
Issue number1
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • General


Dive into the research topics of 'KRASG12D and TP53R167H Cooperate to Induce Pancreatic Ductal Adenocarcinoma in Sus scrofa Pigs'. Together they form a unique fingerprint.

Cite this