Project Details
Projekt
Disrupting spliceosome-licensed oncogene collaboration networks for precision cancer therapy
Subject Area
Gastroenterology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 521659142
Pancreatic Ductal Adenocarcinoma (PDAC) remains a disease with a frustratingly low 5 year survival rate of only 11%. In western countries increasing incidence and mortality rates of PDAC were observed. The current standard of care applies modestly effective combination chemotherapies, which definitely need improvements. Therefore, developing therapeutic options for PDAC is an unmet medical need with a high social impact. The last decade has witnessed a revolution in drug development with the promise to target nearly every protein or cellular machinery. Even the splicing machinery, for which a contribution to the hallmarks of cancer is documented, can be specifically targeted. Splicing inhibitors are already in clinical development. Furthermore, our work demonstrates that splicing is a target in solid cancers, including PDAC. Using two-dimensional Cas13-based genetic interaction screens, a technology developed in our laboratories, in combination with a large cell lines platform covering the relevant splicing-related subtypes, we aim to discover actionable and context-dependent PDAC vulnerabilities, which can be translated into novel splicing-centered combination therapies. We aim to mechanistically understand the vulnerabilities and, via biomarker analysis, translate them into precise splicing-centered combination therapies.
DFG Programme
Research Grants
