Dual RAS/SHP2 inhibition for sensitization of pancreatic cancer to immunotherapy (P17)

• Subject Area: Hematology, Oncology ; General and Visceral Surgery ; Gastroenterology ; Clinical Immunology and Allergology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 441891347

The project investigates if vertical RAS+SHP2 blockade can sensitize PDAC to immunotherapy. Aim 1 is dedicated to identifying immune architectures in human and murine PDAC tissues, with correlation to genetic setup, i.e. mutated KRAS and major tumor suppressor loss. Aim 2 assesses the impact of RAS+SHP2 inhibition on signaling and expression of immunoregulators in PDAC organoids and cell lines, and profiles off-target immune cell specific effects. Based on preliminary data, Aim 3 tests the addition of TGFβR1i/anti-TIM-3 (anti-TIGIT) to vertical RAS+SHP2 blockade in murine and human tumors.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1479: Oncogene-driven immune escape (OncoEscape)
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Heads: Professor Bertram Bengsch, Ph.D., since 1/2026; Privatdozent Dr. Dietrich Ruess