Small molecule-induced reprogramming of pancreatic tumor and stroma compartments

• Applicants: Professor Dr. Thomas Mathias Gress; Professor Dr. Matthias Lauth
• Subject Area: Gastroenterology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 329116008

Project SP2 of the clinical research unit 325 (CRU325) focuses on epigenetic reprogramming of tumor and stroma compartments in order to improve future therapies. Loss of cellular identity/differentiation is a key feature of many cancers including pancreatic ductal adenocarcinoma (PDAC). In this project, we aim to characterize a novel pharmacological approach inflicting pro-differentiating cues on cancer cells. Intriguingly, this treatment is associated with significant reduction in c-MYC levels, a well-established and very potent oncogene in PDAC regulating both, tumor and stroma compartments. These effects result in a sensitization against the common chemotherapeutic drug Gemcitabine and a prominent induction of cell death in PDAC cell lines and primary organoids. Moreover, stromal stellate cells adopt characteristic alterations associated with a tumor-restraining phenotype. In a second CRU325 funding period, we wish to continue this line of research, detailing our understanding of the molecular mechanism of drug action and translating the findings to patient-relevant conditions.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 325: Clinical relevance of tumor-microenvironment interactions in pancreatic cancer