Glypican-3: A New Target for Diagnosis and Treatment of Hepatocellular Carcinoma

Liver cancer is the second leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma is the most common type. The pathogenesis of hepatocellular carcinoma is concealed, its progress is rapid, its prognosis is poor, and the mortality rate is high. Therefore, novel molecular targets for hepatocellular carcinoma early diagnosis and development of targeted therapy are critically needed. Glypican-3, a cell-surface glycoproteins in which heparan sulfate glycosaminoglycan chains are covalently linked to a protein core, is overexpressed in HCC tissues but not in the healthy adult liver. Thus, Glypican-3 is becoming a promising candidate for liver cancer diagnosis and immunotherapy. Up to now, Glypican-3 has been a reliable immunohistochemical marker for hepatocellular carcinoma diagnosis, and soluble Glypican-3 in serum has becoming a promising marker for liquid biopsy. Moreover, various immunotherapies targeting Glypican-3 have been developed, including Glypican-3 vaccines, anti- Glypican-3 immunotoxin and chimeric-antigen-receptor modified cells. In this review, we summarize and analyze the structure and physicochemical properties of Glypican-3 molecules, then review their biological functions and applications in clinical diagnosis, and explore the diagnosis and treatment strategies based on Glypican-3.