Culturing of Circulating Tumor Cells in Pancreatic Cancer Patients for Longitudinal Assessment and Drug Sensitivity Profiling of Circulating Disease

• Applicant: Dr. Darius Halm
• Subject Area: General and Visceral Surgery
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 581555595

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality in Germany, with an overall five-year survival of only 11% primarily due to early systemic dissemination and treatment resistance. Current monitoring strategies rely on serology and cross-sectional imaging. Carbohydrate antigen 19-9 (CA 19-9) is the most used biomarker, yet its sensitivity and specificity is limited. Approximately 10% of patients are Lewis antigen negative and non-expressors for CA 19-9 and even in expressors, CA 19-9 does neither consistently reflect tumor burden nor treatment response. Furthermore, cross-sectional imaging can detect macroscopic lesions, but misses micro-metastases and cannot distinguish viable tumor from treatment-induced fibrosis. Circulating tumor cells (CTCs) are shed from primary tumors and are considered “seeds of metastasis” . Primary tumor cells undergo epithelial-to-mesenchymal transition, acquire stem-like features and display unique phenotypes that enable them to evade immune surveillance and colonize distant organs. Multiple studies across different cancers have demonstrated that CTC biology is distinct from the primary tumor, with evidence of phenotypic heterogeneity and mutational discordance (e.g. in KRAS variants). While substantial efforts have been made to characterize primary tumors, circulating disease remains underexplored. The host institution's preliminary work has established CTCs as clinically relevant biomarkers in PDAC. They identified two CTC subtypes: epithelial (eCTCs) and transitional (trCTCs), which independently predict survival and correlate with increased recurrence risk and worse prognosis. In a prospective trial, long-term survival was only achieved in patients who were trCTC negative or became trCTC negative postoperatively. There are significant challenges in monitoring and treatment of PDAC, especially in detecting and characterizing circulating disease. This postdoctoral fellowship aims to refine CTC culturing with a focus on improving scalability and efficiency for clinical application through evaluation of two different methods of cultivation: 3D Organoids and Chorioallantoic Membrane Cultures. The most promising technique will then be applied to blood samples from PDAC patients with locally advanced or metastatic disease. The second aim will be developing a pipeline for drug sensitivity profiling of CTC cultures from human serum samples and investigating associations between circulating disease biology and observed clinical outcomes.

• DFG Programme: Fellowship
• International Connection: USA
• Host: Professor Dr. Christopher Wolfgang