Glypican-3 (GPC3) Targeted Radiopharmaceuticals for Treatment of Liver Cancer

Glypican-3 (GPC3) is a membrane-bound heparan sulfate proteoglycan. GPC3’s expression is limited during embryonic development and is very low or undetectable in healthy tissues of adults. However, its expression is significantly upregulated in hepatocellular carcinoma (HCC), a major type of liver cancer. The specific expression of GPC3 in tumor tissues renders GPC3 a potential biomarker for diagnosis of HCC, and presents an opportunity for the development of targeted radiopharmaceuticals against HCC. Herein, we review the current understanding of the molecular structure and biology of GPC3, and summarize recent progress in developing GPC3-based imaging and radionuclide therapies against HCC. We categorize imaging and radionuclide therapies into antibody-based and peptide-based molecules and provide our insights into the benefits of each category. We also give our perspectives on the challenges of developing safe and efficacious GPC3-targeted radionuclide therapies for liver cancer.