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Critical analysis of the potential of targeting GPC3 in hepatocellular carcinoma

Authors Ofuji K, Saito K, Yoshikawa T, Nakatsura T

Received 11 March 2014

Accepted for publication 4 April 2014

Published 21 May 2014 Volume 2014:1 Pages 35—42

DOI https://doi.org/10.2147/JHC.S48517

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Kazuya Ofuji, Keigo Saito, Toshiaki Yoshikawa, Tetsuya Nakatsura

Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan

Abstract: 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

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