靶向磷脂酰肌醇蛋白聚糖-3治疗肝细胞癌的临床应用前景

磷脂酰肌醇蛋白聚糖-3（glypican-3, GPC3）是一种锚附着在细胞膜表面的癌胚蛋白质, 在肝细胞癌中过表达。GPC3可以作为肝细胞癌的生物标志物, 肝癌病人的血清GPC3水平对于预后评估存在重要价值。此外, 肝癌细胞中GPC3具有免疫反应性, 可以作为治疗靶点, 有关靶向GPC3治疗肝细胞癌的临床试验已经展开。本文简述了GPC3的结构及其在肝细胞癌发生发展中的作用, 回顾了靶向GPC3治疗肝细胞癌的临床研究结果, 并总结了GPC3相关临床应用的最新进展：新的抗GPC3抗体正在研发, 它们与其它靶向药物联用的临床试验正在展开；有关GPC3靶向的TRAB、GPC3疫苗和GPC3基于嵌合抗原受体(CAR)-T疗法的研究正在进行。我们认为，靶向GPC3治疗肝细胞癌的方案具有广阔的临床应用前景, 期待更多的研究聚焦于此, 为靶向GPC3疗法提供更充分的科学依据。

Prospect of Clinical Application of Glypican-3 Targeted Therapy for Hepatocellular Carcinoma

Glypican-3 (GPC3) is an oncofetal protein anchored on the plasma membrane and highly expressed in hepatocellular carcinoma (HCC). GPC3 could be used as a biomarker for the diagnosis of HCC and the serum levels of GPC3 in liver cancer patients has a significant role for their prognosis. Moreover, GPC3 in HCC cells is immunoreactive, rendering it a suitable target for the treatment of HCC. Nowadays, several clinical trials targeting GPC3 for HCC therapy have already been conducted: new anti-GPC3 antibodies are generated; the clinical trials about its combination administration with other targeted medicines are being in progress; GPC3-targeted TRAB, GPC3 vaccines and GPC3-based chimeric antigen receptor T-cells (CAR-T) therapy are under investigation. In this review, we briefly discuss the structure of GPC3, its role in HCC pathogenesis and summarize the recent development in the clinical application of GPC3. We firmly believe that GPC3 would be a promising target for HCC therapy. And further studies focusing on GPC3 should provide us more solid evidence.