It ranks first among asymptomatic cancers.311 Pancreatic cancer is extremely difficult to detect as it lacks early signs and spreads rapidly to the surrounding organs.311 The high malignancy of pancreatic cancer is mostly attributed to the hypoxic tumor microenvironment.312,313 Pancreatic cancer is accompanied by HIF-1α overexpression.314,315 Herein, we summarized the mechanism by which hypoxia signaling affects the tumorigenesis and progression of pancreatic cancer (Fig. 5). Here, HIF1A is linked to familial pancreatic carcinoma.