In this study, we have found that RUNX2 depletion-mediated further induction of TAp63 improves the cytotoxic effect of GEM on p53-mutated Panc-1 cells (R273H), and thus our present observations strongly suggest that the disruption of the balance between the intracellular endogenous amounts of pro-oncogenic mutant p53 and pro-apoptotic TAp63 might be one of the attractive strategies for the enhancement of GEM efficacy of pancreatic cancer patients. This evidence concerns the gene RUNX2 and familial pancreatic carcinoma.