Ror2, receptor tyrosine kinase-like orphan receptor 2, is a signaling receptor for Wnt ligands. It plays important roles in limb development and is involved in mediating both canonical and non-canonical signaling pathways [3]. Ror2 is expressed in various tissues during development and has been associated with multiple biological processes, making it an important molecule for understanding normal development and disease mechanisms.

In a mouse model of pancreatic tumorigenesis, ablation of Ror2 promoted a switch to a gastric pit cell identity, which persisted through progression to the classical subtype of pancreatic ductal adenocarcinoma (PDAC). In both human and mouse pancreatic cancer, ROR2 activity antagonized the gastric pit cell identity, strongly promoting an epithelial-to-mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition [1]. In prostate cancer organoid culture and xenograft models, WNT5a signaling through ROR2 activated the Hippo pathway to suppress YAP1 activity and tumor growth [2].

In conclusion, Ror2 is a key regulator in multiple biological processes and disease conditions. The gene knockout (KO) and conditional knockout (CKO) mouse models have been crucial in revealing its role in pancreatic neoplasia, adenocarcinoma, and prostate cancer. These findings suggest that Ror2 could be a potential therapeutic target in these diseases.