RSPO1 and familial pancreatic carcinoma: Based on the distinct niche factor dependencies, three subtypes of pancreatic cancer PDOs have been identified: (1) Wnt non-producing subtype requiring Wnt for growth; (2) Wnt producing subtype autonomously secreted Wnt ligands; and (3) R-spondin independent subtype that grows in the absence of Wnt and R-spondin [48].