Progreso de la investigación de fármacos dirigidos a GPC3 en la terapia del cáncer

Glypican-3 (GPC3) is a cell surface heparan sulfate proteoglycan that is silenced in normal adult tissues but aberrantly re-expressed in several cancers, particularly hepatocellular carcinoma (HCC). Its restricted expression pattern and involvement in oncogenic signaling make it an attractive therapeutic target. Recent advances have led to the development of diverse GPC3-directed modalities, including monoclonal and bispecific antibodies, antibody-drug conjugates (ADCs), immunotoxins, peptides, and chimeric antigen receptor (CAR)-engineered immune cells. These approaches have demonstrated promising efficacy and manageable safety profiles in preclinical and early clinical studies. In addition, post-transcriptional regulation of GPC3 by non-coding RNAs has emerged as a key mechanism influencing its expression and tumorigenic potential, providing novel opportunities for RNA-based therapies. This review summarizes current progress in GPC3-targeted drug development, highlights structure-affinity optimization strategies and discusses translational outcomes and emerging combination strategies. The overview offers an integrated perspective to support the rational design of next-generation GPC3-targeted therapeutics in cancer therapy.