U3-1784

In this study, we designed a series of FGFR4-targeted peptide-radionuclide conjugates (PRCs) based on a high-affinity peptide ligand derived from the binding epitope of the monoclonal antibody U3-1784...In xenograft models, this probe demonstrated high uptake (1.89 ± 0.35% ID/g) and produced high-contrast images specifically in high-FGFR4-expressing tumors. These results indicate that 99mTc-HYNIC-FYQ-8 is a promising peptide-based radiotracer for clinical imaging of FGFR4-overexpressing tumors.

These findings demonstrate that HNF1A drives PDAC metastasis via upregulation of FGFR4, and FGFR4 inhibition is a potential mechanism to target metastasis in PDAC patients.

The FGFR4/FGF19 signaling axis is overactivated in 20% of liver tumors and currently represents a promising targetable signaling mechanism in this cancer type. These effects could be completely prevented by the concomitant oral treatment with the bile acid sequestrant colestyramine, which binds and eliminates bile acids in the gut. These results offer a new biomarker-driven treatment modality in liver cancer without toxicity and they suggest a general strategy for avoiding adverse events with FGFR4 inhibitors.