Critical analysis of the potential of targeting GPC3 in hepatocellular carcinoma

• Main Authors: Ofuji K, Saito K, Yoshikawa T, Nakatsura T
• Format: Article
• Language: English
• Published: Dove Medical Press 2014-05-01
• Series: Journal of Hepatocellular Carcinoma
• Subjects: Glypican-3 (GPC3); hepatocellular carcinoma; immunotherapy
• Online Access: https://www.dovepress.com/critical-analysis-of-the-potential-of-targeting-gpc3-in-hepatocellular-peer-reviewed-article-JHC

Kazuya Ofuji, Keigo Saito, Toshiaki Yoshikawa, Tetsuya NakatsuraDivision of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, JapanAbstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. The treatment options for patients with advanced HCC are limited, and novel treatment strategies are required urgently. Glypican-3 (GPC3), a member of the glypican family of heparan sulfate proteoglycans, is overexpressed in 72%-81% of HCC cases, and is correlated with a poor prognosis. GPC3 regulates both stimulatory and inhibitory signals, and plays a key role in regulating cancer cell growth. GPC3 is released into the serum, and so might be a useful diagnostic marker for HCC. GPC3 is also used as an immunotherapeutic target in HCC. A Phase I study of a humanized anti-GPC3 monoclonal antibody, GC33, revealed a good safety profile and potential antitumor activity, and a Phase II trial is currently ongoing. In addition, the authors' investigator-initiated Phase I study of a GPC3-derived peptide vaccine showed good safety and tolerability, and demonstrated that the GPC3 peptide-specific cytotoxic T-lymphocyte frequency in peripheral blood correlated with overall survival in HCC patients. A sponsor-initiated Phase I clinical trial of a three-peptide cocktail vaccine, which includes a GPC3-derived peptide, is also underway. GPC3 is currently recognized as a promising therapeutic target and diagnostic marker for HCC. This review introduces the recent progress in GPC3 research, from biology to clinical impact.Keywords: GPC3, hepatocellular carcinoma, immunotherapy