Targeting Glypican-3 for Liver Cancer Therapy: Clinical Applications and Detection Methods.

Abstract

Recent advancements in cancer immunotherapy have highlighted glypican-3 (GPC3) as a prominent target for treating hepatocellular carcinoma (HCC). However, approximately 10% to 30% of HCC patients exhibit low or absent GPC3 expression on the surface of tumor cells, which limits the feasibility of GPC3-targeted therapies. Consequently, it is essential for patients to undergo pre-diagnostic assessments of GPC3 expression in tumor cells to evaluate their suitability for GPC3-directed therapy. Although various methods have been developed to specifically detect GPC3 as a biomarker for treatment and prognosis, the diagnostic approaches currently employed in clinical studies remain relatively limited. Here, we provide a comprehensive overview of the clinical development of GPC3-targeted therapeutics, clinical trials in GPC3-positive HCC, and current methods for detecting GPC3 expression, highlighting their advantages and limitations. Furthermore, we explore the potential of integrating targeted therapy with various GPC3 detection modalities tailored to different pathological stages. This integration not only provides insights into the selection of effective methods for detecting GPC3 expression but also has the potential to significantly improve the clinical outcomes of patients with liver cancer. By simultaneously assessing the advantages and disadvantages of these methods, this review aims to establish a theoretical foundation for the clinical selection of appropriate GPC3 detection strategies for targeted therapy.