Working group Singh

The 10-year survival rate for patients with pancreatic cancer (PDAC) stands at approximately 1%. While mortality rates for other cancers have significantly declined in recent years, PDAC is projected to become the second leading cause of cancer-related deaths by 2030. In Germany, between 20,000 and 22,000 individuals are diagnosed with PDAC each year, with almost an equal number succumbing to this complex disease during the same timeframe. The incidence and mortality rates of PDAC are closely linked to aging, a major concern in many European nations where populations are rapidly aging. The hallmarks of PDAC include early tumor invasion, with over 80% of cases displaying local or distant metastasis at the time of diagnosis. Unfortunately, among the 20% of patients who undergo surgical resection, many experience local or distant tumor recurrence due to the presence of resilient micro-invasive tumor cells. Currently, the primary treatment option for all PDAC patients consists of surgical resection followed by intensive chemotherapy. However, one-third of these patients experience tumor relapse within three years. Given the limited scope of personalized therapeutic approaches, there is an urgent need for advanced molecular screening-based individualized stratification to enhance overall prognosis in PDAC patients.

Key biomedical challenges in the prognosis and treatment of pancreatic cancer

The intricate molecular heterogeneity present in tumor and stromal immune compartments poses challenges for conventional therapies, contributing to a grim prognosis and complicating patient stratification for treatment. The identification of transcriptomic subtypes has significantly improved early prognosis and therapeutic interventions for PDAC patients. For instance, transcriptomic profiling has revealed two distinct subtypes: 'classical' and 'basal-like.' The basal-like subtype is strongly associated with poorer prognosis and resistance to therapy, while the classical subtype correlates with a more favorable outlook. For further information, please refer to our latest review article published in Trends in Cancer 2022 (PMID: 36117109).

Our Max-Eder research group focuses on advancing personalized medicine and translational cancer research. We believe a deeper understanding of tumor and immune cell differences could improve patient outcomes in PDAC. Our latest study shows how different tumor subtypes interact with immune cells in the tumor environment to drive PDAC aggression. Specifically, we found that the characteristics of tumor cells attract inflammatory macrophages, which push away immune cells that could attack the tumor and make the disease worse. For more details, please refer to our publication in Nature Cancer 2021 (PMID: 35122059), its preview in Cancer Discovery 2022 (PMID: 34862194), and in Nature Communications 2025 (PMID: 39762215).

Additionally, metastatic pancreatic cancer (PDAC) has a poor outlook, with a 5-year survival rate below 3%. We have recently discovered a new factor, the ROBO3 receptor, that helps the cancer spread and become resistant to treatment. By blocking ROBO3 signaling, we can reduce fluid buildup and liver metastases, and restore sensitivity to chemotherapy. This study uncovers an important mechanism behind the aggressive subtype of PDAC and supports treatment strategies that aim to target these subtypes to overcome resistance. For further details, please see our publication in JCI Insight 2022 (PMID: 35993361).