ROR2: A Key Regulator of Cellular Plasticity in Pancreatic Cancer Development and Therapy Resistance

This study identifies ROR2, a receptor tyrosine kinase, as a critical driver of cellular identity and progression in pancreatic ductal adenocarcinoma (PDAC). ROR2 fosters a gastric metaplasia-like identity in precancerous lesions and aids the transformation into aggressive PDAC subtypes. Through single-nucleus ATAC-seq analysis, researchers found that ROR2 promotes an epithelial-to-mesenchymal transition (EMT) that enhances resistance to KRAS inhibitors while increasing sensitivity to AKT inhibitors. ROR2’s presence in tumor cells was linked to mesenchymal differentiation and stemness, both of which drive PDAC’s basal-like, aggressive phenotype. Targeting ROR2 in combination with AKT inhibition may represent a promising strategy to counteract PDAC resistance to traditional therapies.