Fig. 9: Diagram depicts that targeting OTUB1 sensitizes pancreatic cancer to gemcitabine chemotherapy.

OTUB1 interacts and stabilizes DDX3X to enhance DHODH-mediated de novo pyrimidine synthesis, thereby upregulating dCDP and dCTP for efficient DNA replication, reducing gemcitabine-induced replication stress, and conferring gemcitabine resistance in PC.