Our findings indicate that MYC and mTORC pathways are critical driver in HIF-1 high score tumors, which provides a preliminary rationale for combination treatment using HIF-1 inhibitor and MYC inhibitor, or using HIF-1 inhibitor and everolimus in these highly hypoxic and aggressive pancreatic cancers in future studies. Here, HIF1A is linked to familial pancreatic carcinoma.