Pancreatic cancer is one of the most aggressive malignancies worldwide, with a very low survival rate after diagnosis. KRAS mutation is an early event in pancreatic tumorigenesis and is critical for cancer initiation and progression. Elucidating the underlying mechanisms regulating pancreatic organogenesis may help to identify molecular pathways underlying exocrine pancreatic carcinogenesis. The great progress in mouse models of pancreatic cancer has raised expectations, however, the results of preclinical trials of most new drugs that have shown good efficacy against invasive pancreatic ductal adenocarcinoma in mouse models have not been confirmed in the clinical stage. Addressing this fundamental problem may require the development of new animal models.
The zebrafish is an amenable vertebrate model for genetic manipulation, and its pancreas shares many similarities with the human pancreas, including similar transcription factors and genetic networks for pancreatic development and function. Therefore, zebrafish is a suitable in vivo model to study pancreatic cancer. Various approaches using forward and reverse genetics, chemical genetics, and transgenes in zebrafish have demonstrated universally conserved regulation of mammalian genes and uncovered novel genetic pathways in exocrine pancreas development. Growing evidence supports the use of zebrafish as a model for human malignant disease, including pancreatic cancer. The study demonstrates that genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets for human pancreatic cancer.
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