Project Summary
In P21N, we aim to investigate whether oncogenic signalling in KRAS-G12D PDAC drives COX pathway activity and how this determines cancer immune escape. In Aim 1, we will characterize the cell-intrinsic consequences of KRAS-G12D oncogenic signalling in PDAC and explore how this is linked to PGE2 production and aberrant COX pathway activity. In Aim 2, we plan to determine whether interference with the COX-PGE2-EP2/EP4 axis can restore anti-cancer T-cell immunity in KRAS-G12D PDAC and promote cancer immune control. In Aim 3, we will study the clinical relevance of our findings using patient samples and organoid systems.
