Porcine Models of Pancreatic Cancer.

Abstract

Pancreatic cancer is the fourth most common cause of cancer-related deaths in both men and women. The 5-year survival rate for metastatic pancreatic cancer is only 8%. There remains a need for improved early diagnosis and therapy for pancreatic cancer. Murine models are the current standard for preclinical study of pancreatic cancer. However, mice may not accurately reflect human biology because of a variety of differences between the two species. Remarkably, only 5–8% of anti-cancer drugs that have emerged from preclinical studies and entered clinical studies have ultimately been approved for clinical use. The cause of this poor approval rate is multi-factorial, but may in part be due to use of murine models that have limited accuracy with respect to human disease. Murine models also have limited utility in the development of diagnostic or interventional technology that require a human-sized model. So, at present, there remains a need for improved animal models of pancreatic cancer. The rationale for a porcine model of pancreatic cancer is (i) to enable development of diagnostic/therapeutic devices for which murine models have limited utility; and (ii) to have a highly predictive preclinical model in which anti-cancer therapies can be tested and optimized prior to a clinical trial. Recently, pancreatic tumors were induced in transgenic Oncopigs and porcine pancreatic ductal cells were transformed that contain oncogenic KRAS and p53-null mutations. Both techniques to induce pancreatic tumors in pigs are undergoing further refinement and expansion. The Oncopig currently is commercially available, and it is conceivable that other porcine models of pancreatic cancer may be available for general use in the near future.