In conclusion, our current findings strongly suggest that depletion of RUNX2 improves GEM sensitivity of p53-mutated pancreatic cancer Panc-1 cells in a TAp63-dependent manner, and thus our present study might provide a novel strategy to enhance the cytotoxic efficacy of GEM on aggressive and metastatic pancreatic cancer patients with p53 mutation. This evidence concerns the gene TP53 and pancreatic neoplasm.