Acinar cell specific susceptibility for tumor development in the pancreas: target the critical regulators for therapy

Pancreatic cancer is one of the deadliest tumors. We need a better understanding of the biology of this tumor before we can improve patient outcomes.
In conditions of inflammation, one cell type of the exocrine pancreas becomes susceptible to tumor formation while another cell type remains more resistant. Strikingly, the one cell type (acinar cells) becomes susceptible while gaining many characteristics of the resistant duct cell type. Previous work focused on the acquired similarities. Now want to investigate specifically how the susceptible dedifferentiated acinar cells, albeit duct-like, differ from the duct cells, because this may hold new keys to develop novel therapies. We will assess two genes of interest (transcription factors since
they have a broader regulatory role) in a pipeline of experimental mouse models that allow studying effects on cell differentiation, tumor development and tumor progression. In preliminary work with human cells, we already identified one promising transcription factor that needs further study. Another will be prioritized in the course of the project. We aim to discover novel targets that might be amenable for therapy, not only for suppressing tumor development in high-risk individuals but also for treatment of patients who already have a tumor. A first assessment of the therapeutic potential of the new drugable targets is included in the study.