Liver cancer is the second leading cause of cancer‐related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican‐3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis. Mechanistic studies have revealed that GPC3 functions in HCC progression by binding to molecules such as Wnt signaling proteins and growth factors. Moreover, GPC3 has been used as a target for molecular imaging and therapeutic intervention in HCC. To date, GPC3‐targeted magnetic resonance imaging, positron emission tomography, and near‐infrared imaging have been investigated for early HCC detection, and various immunotherapeutic protocols targeting GPC3 have been developed, including the use of humanized anti‐GPC3 cytotoxic antibodies, treatment with peptide/DNA vaccines, immunotoxin therapies, and genetic therapies. In this review, we summarize the current knowledge regarding the structure, function, and biology of GPC3 with a focus on its clinical potential as a diagnostic molecule and a therapeutic target in HCC immunotherapy.

中文翻译：

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Glypican-3：肝细胞癌诊断和治疗的有前途的生物标志物

肝癌是癌症相关死亡的第二大主要原因，而肝细胞癌（HCC）是最常见的类型。因此，迫切需要分子靶标来早期检测HCC和开发新的治疗方法。Glypican-3（GPC3）是一种锚固在细胞膜上的胎粪蛋白聚糖，通常在胎儿肝脏中检出，而在健康的成年肝脏中则未检出。然而，在HCC患者中，GPC3在基因和蛋白质水平上均过表达，其表达预后不良。机理研究表明，GPC3通过与Wnt信号蛋白和生长因子等分子结合而在HCC进程中发挥作用。此外，GPC3已被用作肝癌分子成像和治疗干预的靶标。迄今为止，以GPC3为目标的磁共振成像，已对正电子发射断层扫描和近红外成像进行了研究，以进行早期HCC检测，并且已开发出多种针对GPC3的免疫治疗方案，包括使用人源化抗GPC3细胞毒性抗体，肽/ DNA疫苗治疗，免疫毒素疗法和遗传疗法。在这篇综述中，我们总结了有关GPC3的结构，功能和生物学的最新知识，重点是其作为HCC免疫治疗中的诊断分子和治疗靶标的临床潜力。