Mechanisms of bloodborne tumor cell dissemination and metastasis in pancreatic cancer

• Applicants: Professor Dr. Simon Anders; Privatdozentin Dr. Susanne Roth, since 9/2023
• Subject Area: General and Visceral Surgery
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497768044

Pancreatic cancer is a devastating disease with an exceptionally poor prognosis. Subclinical metastasis might occur early during tumor development, but iatrogenic tumor cell dissemination during surgery is also a concern. High levels of circulating tumor cells (CTCs) have been associated with tumor progression and poor prognosis in pancreatic cancer patients. CTCs serve as precursors of metastasis in several types of solid cancer, and CTC clusters constitute an exceptionally highly metastasis-competent subset of CTCs. Determining the biological features and mechanisms of those CTCs that survive in the bloodstream and initiate metastases (via single-cell sequencing) might improve our understanding of the metastatic process in pancreatic cancer. Within a prospective clinical trial peripheral and portal venous blood, as well as pancreatic tissue will be collected from pancreatic cancer patients at different time points (before, during and after surgery). This will enable us to a.) determine the mechanisms of bloodborne dissemination of pancreatic cancer and potential differences between spontaneously released CTCs and CTCs shed during surgical tumor resection, b.) assess the composition of CTCs in pancreatic cancer by comparing molecular profiles of CTCs with matched primary tumors, c.) identify mechanisms of CTC cluster formation and potential druggable vulnerabilities. These investigations might enable the design of novel treatment strategies that hamper the metastatic process of this devastating disease.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Thilo Hackert, until 9/2023