RSPO1 and pancreatic neoplasm: Canonical WNT ligands, such as Wnt family member 2, Wnt family member 5A, and Wnt family member 7A, have been observed to be increased in pancreatic cancer tissues, and activated the WNT pathway, leading to the progression of pancreatic cancer.104,105 In addition, noncanonical ligands, such as mucin (MUC) family members (MUC1 and MCU4) and R-spondin, activate the WNT pathway, leading to pancreatic cancer progression.106–108 Pancreatic cancer is characterized by hypoxic conditions.