Targeting the prohibitin scaffold-CRAF kinase interaction in RAS-ERK-driven pancreatic ductal adenocarcinoma.

Background Robust ERK1/2 activity, which frequently results from KRAS mutation, invariably occurs in pancreatic ductal adenocarcinoma (PDAC). However, direct interference of KRAS signaling has not led to clinically successful drugs. Correct localization of RAF is regulated by the scaffold protein prohibitin (PHB) that ensures the spatial organization between RAS and RAF in plasma membranes, thus leading to activation of downstream effectors.