Fischer and colleagues demonstrated that in colorectal cancer PDX models, monoclonal antibodies targeting RSPO3 (a potent Wnt-signaling enhancer that binds LGR5 to potentiate Wnt activation by reducing Wnt-receptor turnover) had a strong synergistic effect against tumor growth when administered in combination with paclitaxel (83). Here, LGR5 is linked to colorectal cancer.