At present,pancreatic ductal adenocarcinama (PDAC) is one of the deadliest malignant solid tumors,with poor prognosis and 5-year survival rate of 5％.Although understanding of the pathogenesis has greatly been improved for nearly two decades,there isn't a breakthrough in clinical therapy of the PDAC,and finding a new and effective therapy is badly needed.Genetic analysis showed that KRAS was one of the earliest and great probability mutated gene in the PDAC,played a significant role in initiation,progression,and metastasis of cancer,and predicted to being a good target of anti-PDAC.But a KRAS-targeted effective drug is lacking in clinic.The direct KRAS-targeted therapy will bright prospects.Meanwhile,locking localization and activity of cell membrane through post-translational modifications to KRAS combined with inhibiting KRAS downstream pathway is a good way of the KRAS-targeted PDAC therapy.