Modelling and targeting pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is almost always fatal and has the highest mortality rate of all solid tumor entities. The annual number of deaths equals the number of newly diagnosed cases despite maximal treatment. The overall 5-year survival rate of less than 8% has remained almost unchanged over the last 30 years, despite tremendous efforts in preclinical and clinical science. The abysmal prognosis of PDAC is compounded by its increasing incidence in the western world; PDAC is predicted to become the second leading cause of cancer death in the next decade.

The overarching goal of this collaborative research consortium is to gain a holistic mechanistic understanding of PDAC, to explain why it resists conventional and targeted therapies and thereby pave the way to novel effective treatments for this devastating disease. The poor prognosis of PDAC is due to a unique combination of several biological features that set it apart from other tumor entities. These include cellular plasticity, huge tumor heterogeneity with many molecular subtypes, a dense tumor stroma that harbors a complex immunosuppressive microenvironment, a singular macroenvironment with perineural invasion, cachexia, thrombosis, early metastasis and a set of signaling pathways activated by the driving oncogene KRAS. It is likely that all these features contribute individually and through cellular and molecular interplay to the unique biology and therapy refractory nature of the disease. We are convinced that a holistic and integrated research approach is required to functionally dissect and understand these malignant networks, and have therefore assembled a consortium of scientists with unique and complimentary expertise from different disciplines to understand PDAC. As outlined below, our collaborative research center (CRC) will achieve this goal through integrating diverse research fields and novel technologies as well as through extensive interdisciplinary collaboration.

Our efforts range from global unbiased genomic, epigenomic, proteomic and metabolomic analyses and genetic and pharmacological screens to hypothesis-driven mechanistic studies. Our experimental systems include unique collections of well-characterized human PDAC tumors and cell lines as well as genetically defined mouse PDAC cell systems, organoids and sophisticated mouse and pig PDAC models. This collaborative multidisciplinary consortium of experts focused solely on unraveling the biology of pancreatic cancer will enable us to identify and exploit novel therapeutic vulnerabilities.