Animal models and cell lines of pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs), also known as islet cell tumors, are mostly indolent neoplasms that probably arise from a network of endocrine cells that includes islet cells and pluripotent precursors in the pancreatic ductal epithelium. The incidence and prevalence of PNETs continue to rise in recent years because of more sensitive detection. The molecular pathogenesis, early detection, molecular predictors of tumor behavior, and targeted drug therapy of PNETs are not well understood and require additional basic and translational research. The rarity and indolent nature of these tumors, difficulty of access to appropriate patient tissue samples, and varying histopathology and secreted hormones pose particular challenges to PNET researchers. Animal models and cell lines are indispensable tools for investigating the pathogenesis, pathophysiology, mechanisms for tumor invasion and metastasis, and therapeutics of PNETs. This review summarizes currently available animal models and cell lines of PNETs, which have provided valuable insights into the pathogenesis and natural history of human PNETs. In the future, animal models and cell lines of PNETs should also be used to study early tumor detection and molecular predictors of tumor behavior and to test the responses to, and mechanisms for, novel targeted drug therapies.