Druggable cancer cell-intrinsic regulators of extracellular communication

• Applicant: Professor Dr. Matthias Lauth
• Subject Area: Gastroenterology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499289944

Even today, pancreatic ductal adenocarcinoma (PDAC) represents one of the most lethal malignancies with a 5-year survival rate of under 10%. Estimations predict pancreatic cancer to become the 2nd leading cause of death by cancer in the US by 2030. One of the characteristics of the disease is a prominent histological desmoplasia accompanying a pronounced local immune suppression. Tumor cells communicate with immune cells through multiple ways and promote the formation of this immune privilege. Our functional as well as mechanistic understanding of these processes are however insufficient in order to design novel therapeutic approaches. In own previous work, we could show that the tumor cell specific ablation of the PDAC-overexpressed DYRK1B kinase results in defects in extracellular communication. As a result, cancer cells release strongly reduced numbers of extracellular vesicles (EVs) and alter the differentiation of macrophages, eventually culminating in the significant remodeling of the tumor stroma and the blockade of in vivo PDAC growth. In this project, we aim to delineate the molecular mechanisms linking DYRK1B with EVs and the tumor secretome in order to enable us to harness these processes in future therapeutic approaches.

• DFG Programme: Research Grants