Glypican-3(GPC3)is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol.Whereas GPC3 is abundant in fetal liver,its expression is hardly detectable in adult liver.Importantly,GPC3is o...Glypican-3(GPC3)is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol.Whereas GPC3 is abundant in fetal liver,its expression is hardly detectable in adult liver.Importantly,GPC3is overexpressed in hepatocellular carcinoma(HCC),and several immunohistochemical studies reported that overexpression predicts a poorer prognosis for HCC patients.Therefore,GPC3 would serve as a useful molecular marker for HCC diagnosis and also as a target for therapeutic intervention in HCC.Indeed,some immunotherapy protocols targeting GPC3 are under investigations;those include humanized anti-GPC3cytotoxic antibody,peptide vaccine and immunotoxin therapies.When considering the clinical requirements for GPC3-targeting therapy,companion diagnostics to select the appropriate HCC patients are critical,and both immunohistochemical analysis of tissue sections and measurement of serum GPC3 level have been suggested for this purpose.This review summarizes current knowledge regarding the clinical implication of GPC3detection and targeting in the management of patients with HCC.展开更多
基金Supported by Collaborative Research Fund from Chugai Pharmaceutical Co. (to Kataoka H)Grant-in-Aid from The Ministry of Education, Culuture, Sports, Science and Technology, Japan, No. 24390099 (to Kataoka H)
文摘Glypican-3(GPC3)is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol.Whereas GPC3 is abundant in fetal liver,its expression is hardly detectable in adult liver.Importantly,GPC3is overexpressed in hepatocellular carcinoma(HCC),and several immunohistochemical studies reported that overexpression predicts a poorer prognosis for HCC patients.Therefore,GPC3 would serve as a useful molecular marker for HCC diagnosis and also as a target for therapeutic intervention in HCC.Indeed,some immunotherapy protocols targeting GPC3 are under investigations;those include humanized anti-GPC3cytotoxic antibody,peptide vaccine and immunotoxin therapies.When considering the clinical requirements for GPC3-targeting therapy,companion diagnostics to select the appropriate HCC patients are critical,and both immunohistochemical analysis of tissue sections and measurement of serum GPC3 level have been suggested for this purpose.This review summarizes current knowledge regarding the clinical implication of GPC3detection and targeting in the management of patients with HCC.