Glypican-3(GPC3)is a tumor-associated antigen that is specifically expressed in hepatocellular carcinoma(HCC)and having relatively low levels in normal tissues.This unique expression pattern positions GPC3 as a potent...Glypican-3(GPC3)is a tumor-associated antigen that is specifically expressed in hepatocellular carcinoma(HCC)and having relatively low levels in normal tissues.This unique expression pattern positions GPC3 as a potential target for precision therapy and drug development in HCC.Recent studies have shown significant advancements in GPC3-targeted therapies and immunotherapies,particularly for patients with advanced or treatment-resistant HCC.Although certain clinical trials have yielded suboptimal results,numerous ongoing studies continue to explore its therapeutic efficacy.This mini-review focuses on the latest research developments regarding GPC3 as a therapeutic target across various HCC treatment strategies,including monoclonal antibodies,bispecific antibodies,chimeric antigen receptor-T-cell therapies,and other innovative approaches.In addition,the limitations of GPC3-targeted therapies and their future application prospects in HCC treatment are discussed.The review particularly emphasizes the unmet need for future research directions,such as combination immuno-therapy strategies and novel drug designs.Through the integration of innovative technologies and clinical validation,GPC3 holds strong potential as a promising breakthrough in the treatment of HCC,offering new opportunities for enhancing patient outcomes and improving therapeutic efficacy.展开更多
Objective： To investigate the expression of Glypican-3 gene in （α-fetoprotein （AFP）-negative hepatocellular carcinoma （HCC） and clarify whether Glypican-3 expression is a useful parameter for the diagnosis of h...Objective： To investigate the expression of Glypican-3 gene in （α-fetoprotein （AFP）-negative hepatocellular carcinoma （HCC） and clarify whether Glypican-3 expression is a useful parameter for the diagnosis of hepatocelhllar carcinoma （HCC）, especially for AFP-negative ones. Methods： Forty-one specimens of AFP-negative hepatocellular carcinoma and para-carcimoma tissue were studied for the expression of Glypican-3 by Northern blot. The expression of Glypican-3 protein was detected immunohistochemically with specific polyclonal antibody. Results： Northern blot analysis indicated that the expression of Glypican-3 mRNA was intensively detected in 30 of 41 AFP-negative HCC （73.17%）. In contrast, Glypican-3 mRNA was only weakly detected in 4 of the surrounding non-tumor liver tissues. There was significant difference in the Glypican-3 mRNA expression in large tumors （〉5 cm） （79.31%） and in small tumors （〈5 cm） （41.67%） （P〈0.01）. Gypican-3 mRNA was more frequently overexpressed in poorly differentiated HCC than in well differentiated ones （76.47% vs. 42.86%, P〈0.05）. The Glypican-3 expression was not correlated with age. sex. ttbsAg seropositivity, fibroeapsule, portal venous embolus and intrahepatic metastasis. The overexpression of Glypican-3 protein in HCC was targeted in tumor cells, not in bile duct cells and other interstitial cells. Conclusion： Glypican-3 was specially overexpressed in AFP-negative HCC, and its expression was closely correlated with the tumor size and tumor grade. Glypican-3 gene may play important roles in hepatocareinogenesis, and can be used as a new biochemical marker of HCC, especially for AFP-negative HCC.展开更多
文摘Glypican-3(GPC3)is a tumor-associated antigen that is specifically expressed in hepatocellular carcinoma(HCC)and having relatively low levels in normal tissues.This unique expression pattern positions GPC3 as a potential target for precision therapy and drug development in HCC.Recent studies have shown significant advancements in GPC3-targeted therapies and immunotherapies,particularly for patients with advanced or treatment-resistant HCC.Although certain clinical trials have yielded suboptimal results,numerous ongoing studies continue to explore its therapeutic efficacy.This mini-review focuses on the latest research developments regarding GPC3 as a therapeutic target across various HCC treatment strategies,including monoclonal antibodies,bispecific antibodies,chimeric antigen receptor-T-cell therapies,and other innovative approaches.In addition,the limitations of GPC3-targeted therapies and their future application prospects in HCC treatment are discussed.The review particularly emphasizes the unmet need for future research directions,such as combination immuno-therapy strategies and novel drug designs.Through the integration of innovative technologies and clinical validation,GPC3 holds strong potential as a promising breakthrough in the treatment of HCC,offering new opportunities for enhancing patient outcomes and improving therapeutic efficacy.
基金This work was supported in part by grants from the State Key Basic Research Program (No.39825114) and the NationalNatural Science Foundation of China (No.39770379).
文摘Objective： To investigate the expression of Glypican-3 gene in （α-fetoprotein （AFP）-negative hepatocellular carcinoma （HCC） and clarify whether Glypican-3 expression is a useful parameter for the diagnosis of hepatocelhllar carcinoma （HCC）, especially for AFP-negative ones. Methods： Forty-one specimens of AFP-negative hepatocellular carcinoma and para-carcimoma tissue were studied for the expression of Glypican-3 by Northern blot. The expression of Glypican-3 protein was detected immunohistochemically with specific polyclonal antibody. Results： Northern blot analysis indicated that the expression of Glypican-3 mRNA was intensively detected in 30 of 41 AFP-negative HCC （73.17%）. In contrast, Glypican-3 mRNA was only weakly detected in 4 of the surrounding non-tumor liver tissues. There was significant difference in the Glypican-3 mRNA expression in large tumors （〉5 cm） （79.31%） and in small tumors （〈5 cm） （41.67%） （P〈0.01）. Gypican-3 mRNA was more frequently overexpressed in poorly differentiated HCC than in well differentiated ones （76.47% vs. 42.86%, P〈0.05）. The Glypican-3 expression was not correlated with age. sex. ttbsAg seropositivity, fibroeapsule, portal venous embolus and intrahepatic metastasis. The overexpression of Glypican-3 protein in HCC was targeted in tumor cells, not in bile duct cells and other interstitial cells. Conclusion： Glypican-3 was specially overexpressed in AFP-negative HCC, and its expression was closely correlated with the tumor size and tumor grade. Glypican-3 gene may play important roles in hepatocareinogenesis, and can be used as a new biochemical marker of HCC, especially for AFP-negative HCC.
