These results demonstrate that SIRT3 may play an important role in affecting the sensitivity of pancreatic cancer cells to the KRASG12D inhibitor, and suggest that the down-regulation of SIRT3 by KRASG12D may be an intrinsic mechanism by which pancreatic cancer cells harboring KRASG12D resists its own inhibitor. This evidence concerns the gene SIRT3 and familial pancreatic carcinoma.