Furthermore, the presence of RSPO-1 in cell culture media influenced the Wnt–pS6R negative feedback loop in both non-APC (CRC-normal mucosae) and APC-mutated (familial adenomatous polyposis—normal mucosae) PDOs, suggesting that the composition of PDO culture media should be carefully considered when studying the interplay of molecular pathways [98]. Here, APC is linked to colorectal carcinoma.