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Disease progression model of pancreatic cancer developed by Penn researchers

Building on previous work, researchers at the University of Pennsylvania School of Medicine have developed an animal model of pancreatic cancer that closely mimics disease progression in humans. From this, they hope to develop new treatments for this deadly disease. Advanced pancreatic cancer is among the most lethal of cancers, with a one-year survival rate after chemotherapy of only 17 to 28 percent of patients, according to the National Cancer Institute.

Sunil R. Hingorani, MD, PhD, and David A. Tuveson, MD, PhD, both in the Departments of Medicine and Cancer Biology, and colleagues, engineered mice to express two mutant genes commonly associated with pancreatic cancer: Kras, an oncogene, and p53, a well-studied tumor suppressor. The investigators linked physiological, cellular, and genomic changes due to mutations in Kras and p53 in the mice to changes similar to that observed in pancreatic cancer patients. They report their findings in the May issue of Cancer Cell.

The disease that develops in the Kras and p53 mutant mouse model demonstrates distinct similarities to human pancreatic cancer at multiple levels. "In terms of clinical presentation, metastatic burden, and histological changes in tissue, this model appears to closely mimic the human disease," says Hingorani.

Clinical symptoms in the mutant mice mirrored those displayed in pancreatic cancer patients, such as abdominal swelling and muscle loss. Similarly, the progression of pancreatic cancer metastases paralleled that seen in the human disease. "In this model, pancreatic cancer metastasizes to the liver, lungs, diaphragm, and adrenal glands, all the same places that human pancreatic cancer metastasizes," says Tuveson.

The frequency of metastases to these various organ sites was also highly similar to that seen in humans. In human patients, 60 to 80 percent develop metastases to the liver; and 50 to 60 percent develop metastases to the lungs. In the genetically modified an
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Source:University of Pennsylvania


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