EPAS1 and familial pancreatic carcinoma: The Wnt/β-catenin pathway is also implicated in the initiation and progression of pancreatic cancer.97 Hypoxia-inducible factor-2α (HIF-2α) is a transcription factor expressed early in pancreatic lesions that regulates WNT signaling by maintaining β-catenin levels during PanIN progression.98 Moreover, hypoxic conditions in pancreatic tumors stabilize HIF-2α, which cross talks with β-catenin, thereby promoting metabolic reprogramming and PDAC progression.99