Figure 1.

Mimicking human tumorigenesis through temporal modeling of pancreatic cancer. A key difference between human pancreatic cancer and commonly used mouse models is in the timing of mutations. In human patients, Kras mutations are often considered an initiating event, occurring in adult cells, soon followed by mutations to p16, and later p53 and/or SMAD4. Yet in most models, Kras and altered tumor suppressor genes are induced simultaneously in the developing embryo. Despite a human-like histotype, these models have yet to be accurate predictors of outcomes observed in clinical trials. Therefore, we propose that using combinations of several systems to drive sequential Kras, p16, and SMAD4/p53 mutations may lead to more human-like disease that responds to therapy more like that observed in the clinic.