Coordination Funds

• Applicant: Professor Dr. Matthias Lauth
• Subject Area: Gastroenterology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 329116008

Despite significant research efforts in the last decades, pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancer types known. One hallmark of PDAC is its desmoplastic nature characterized by a high content of extracellular material deposition and the presence of numerous stromal cells. Another, more functional hallmark represents the profound immune evasion of PDAC which is reflected by the inherent resistance to immune therapies. It is now undisputed that stromal cells are major determinants of the biology of pancreatic cancer. As such, they represent central players regulating the outspoken aggressiveness of PDAC with its early propensity for metastasis, its high degree of chemoresistance and the significant local host immune suppression. During its first funding period, the Clinical Research Unit 325 (CRU325) has shed light on these fundamental features of the disease and has made exciting progress in the elucidation of pathological mechanisms involved in the crosstalk of pancreatic tumor and stroma compartments. This scientific advancement was made possible by the participating CRU members successfully establishing a highly synergistic and productive structural framework, supported by strong central technology projects and resources.In this renewal proposal we aim to continue this line of research, developing translatable approaches to target different stromal/immune cell populations and their corresponding signaling systems by using a sophisticated array of well standardized patient material, mouse models and in vitro systems. Furthermore, studies on the microbiome and its interplay with host cells have been newly added to our research portfolio. Again, the availability of a central PDAC biosample repository, well-characterized by next generation sequencing including transcriptomics and PDAC driver gene mutation analysis as well as by immune phenotyping and expert histological assessment will be of paramount importance for the success of the subprojects. Establishment of patient-derived cancer organoids as well as animal handling will be carried out centrally to ensure the highest comparability of data obtained in the different CRU projects. These activities will be supported by three central projects covering patient sample biobanking, pathology and in vivo imaging. We expect that the CRU’s translational approach will lead to clinically relevant new insights into the mechanisms and molecules associated with therapy failure in PDAC. In addition, the CRU has structured and integrated research on tumor-microenvironment interactions in PDAC at the local medical faculty and has given important new impetus for new research activities in this area. In summary, due to the close cooperation between basic and clinical science PIs, the CRU is well positioned to achieve its long-term goal of translating preclinical research findings into the clinic in order to improve diagnosis and treatment of PDAC patients.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 325: Clinical relevance of tumor-microenvironment interactions in pancreatic cancer
• Co-Investigator: Professor Dr. Thomas Mathias Gress