In the present study, we evaluated whether the combination of the EZH2 methyltransferase inhibitor, Valemetostat, and the HDAC inhibitor, SAHA, could reduce the interaction of mutp53 with INHAT while enhancing that with p300, resulting in increased acetylation and destabilization of mutp53 in pancreatic cancer cells harboring various p53 mutations. Here, TP53 is linked to familial pancreatic carcinoma.