First animal model for pancreatic cancer may lead to early detection of disease

December 10, 2003

Scientists have made a major discovery that may revolutionize the detection and treatment of one of the most deadly cancers known to man. The research, published online in Cancer Cell, describes the creation and characterization of the first animal model for ductal pancreatic cancer and provides extraordinary insight into development of future diagnostic tests for early disease detection as well as potential therapeutic strategies.

Pancreatic cancer is an aggressive and highly lethal cancer, with a less than 5% chance of surviving just five years past diagnosis. The disease begins to spread almost immediately, making treatment nearly impossible. Understanding the pathology of how pancreatic cancer develops is essential to finding a way to prevent or treat this disease. Drs. Sunil R. Hingorani and David A. Tuveson from the Abramson Family Cancer Research Institute at the University of Pennsylvania genetically engineered mice to express a mutant gene, KRAS, which is commonly associated with pancreatic cancer. The mice developed pancreatic intraepithelial neoplasms (PanIN), a condition that preceded development of full-blown invasive pancreatic cancer. Interestingly, coauthors Drs. Emanuel F. Petricoin and Lance A. Liotta at the FDA/NCI observed that the mice with PanINs had a unique group of proteins in their blood that were not found in disease-free mice. This protein signature provided an accurate and noninvasive means to detect early pancreatic cancer in mice, showing that in principle such an approach could work in humans at high risk for developing pancreatic cancer.

The mice represent the very first animal model that faithfully mimics noninvasive and invasive pancreatic ductal cancer. They also provide solid evidence that PanINs are a precursor to invasive pancreatic cancer. Perhaps one of the most significant findings is the complement of proteins that are unique to the blood of animals with PanINs. "There are currently no tests with sufficient sensitivity and specificity to detect pancreatic cancer early enough to attempt a cure, and no test of any kind exists to identify premalignant disease. Because of the super-aggressive nature of this disease, the only hope for cure comes from the ability to identify the preinvasive condition. Our research identifies a protein signature that can signal the earliest stage of this disease and may even be useful to identify therapeutic targets in pancreatic cancer," explains Dr. Tuveson.
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Cell Press

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