The KPC model of pancreatic ductal adenocarcinoma
Our laboratory utilizes a variety of genetically engineered mouse models of pancreatic cancer. However, the principle model utilized in the Mouse Hospital is the KrasLSL.G12D/+; p53R172H/+; PdxCretg/+ (or KPC) model, a well-validated, clinically relevant model of PDA.(1) KPC mice develop a spectrum of premalignant lesions called Pancreatic Intraepithelial Neoplasia (PanINs) that ultimately progresses to overt carcinoma with 100% penetrance. The tumors generally have a moderately differentiated ductal morphology with extensive stromal desmoplasia, similar to the most common morphology observed in humans. Metastases are observed in 80% of KPC mice, primarily in the liver and lungs, the same sites most commonly observed in humans. The tumors exhibit numerous immunohistochemical markers of PDA and harbor complex genomic rearrangements indicative of genomic instability. Furthermore, KPC mice develop the co-morbidities associated with human PDA such as cachexia, jaundice and ascites. Finally, pancreatic tumors in KPC mice are predominantly resistant to chemotherapy, with only 12% of tumors demonstrating a change in growth kinetics after treatment with gemcitabine.(2)
1.S. R. Hingorani et al., Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7, 469 (May, 2005).
2.K. P. Olive et al., Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324, 1457 (Jun 12, 2009).
1.S. R. Hingorani et al., Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7, 469 (May, 2005).
2.K. P. Olive et al., Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324, 1457 (Jun 12, 2009).
