Glypican (GPC) (GPC)

Glypicans are a family of six cell-surface heparan sulfate proteoglycans (GPC1-6) characterized by a core protein linked to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor (UniProt). They function as essential regulators of cell signaling by interacting with various growth factors and morphogens, such as Wnt, Hedgehog, and Fibroblast Growth Factors, thereby influencing cell proliferation and differentiation (PubMed: 25107346). While their expression is tightly regulated during development and often minimal in adult tissues, certain glypicans like GPC3 are significantly upregulated in cancers, particularly hepatocellular carcinoma (PubMed: 30107174). This tumor-specific expression profile has established glypicans as high-priority therapeutic targets for biologics, including monoclonal antibodies and chimeric antigen receptor (CAR) T-cell therapies (PubMed: 29435137). Therapeutic strategies primarily focus on inducing immune-mediated destruction of tumor cells or inhibiting the growth-promoting signaling pathways facilitated by these proteoglycans. Clinical trials are currently evaluating several GPC-targeted agents, highlighting their potential as both diagnostic biomarkers and therapeutic vulnerabilities in oncology (NIH: NCT02905201).

Other names

Heparan sulfate proteoglycanGPI-anchored proteoglycanGPCHSPG

Glypican-targeted therapies primarily utilize antibody-dependent cellular cytotoxicity (ADCC), T-cell redirection via bispecific antibodies, or direct cytotoxicity through CAR-T cells to eliminate malignant cells. Additionally, some agents may work by neutralizing the ability of glypicans to act as co-receptors for oncogenic growth factors like Wnt and FGF.