{"entity":{"id":"gpc3","kind":"target","name":"Glypican-3","aka":[],"tldr":"Glypican-3 is a fetal liver protein that reappears in liver cancer, giving CAR-T and bispecifics a clean target.","summary":"Glypican-3 is a heparan sulfate proteoglycan that modulates Wnt and Hedgehog signalling; it is a fetal liver protein expressed in 70-80% of hepatocellular carcinoma and essentially absent from normal adult liver, which gives cell and bispecific therapies a clean target. It is also found in hepatoblastoma and yolk-sac tumours. Antibodies failed as monotherapy (codrituzumab), suggesting that simply binding GPC3 is not enough. GPC3 CAR-T, including armoured constructs from AstraZeneca/Neogene and Chinese groups, and GPC3×CD3 bispecifics are showing responses, though durability and the hostile liver microenvironment remain concerns. The simple version is a liver-development protein that reappears in liver cancer, letting engineered immune cells recognise the tumour.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Glypican_3","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Glypican_3"}],"tags":["car-t-target"],"related":[],"cancers":["hcc"],"sections":[],"technologies":[],"targets":[],"drugs":["azd9793"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"GPC3","role":[],"sources":[],"specificity":"tumour-associated","distribution":"one-type","specificityNote":"Tumour-associated overexpression: 1 cell-killing or cell-finding medicine (AZD9793) aim at the antigen, which HPA finds with no normal tissue stained high; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA GPC3: RNA tissue enriched (placenta 670 nTPM); no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Hepatocellular carcinoma); Open Targets associates it with 1 specific cancer type at or above 0.5 (Wilms tumor 1). (Rule 5 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas GPC3 tissue","url":"https://www.proteinatlas.org/ENSG00000147257-GPC3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas GPC3 pathology","url":"https://www.proteinatlas.org/ENSG00000147257-GPC3/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000147257 associations","url":"https://platform.opentargets.org/target/ENSG00000147257/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:4451","ensembl":"ENSG00000147257","uniprot":"P51654","entrez":"2719","firstDescribed":1996,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Pilia et al, Nat. Genet, 1996, \"Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8589713/","biology":"Glypican-3 is a heparan sulfate proteoglycan modulating Wnt and Hedgehog signalling.","whereFound":["Hepatocellular carcinoma","Hepatoblastoma","Yolk-sac tumours"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"hcc","pct":"70-80","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/Glypican_3"}]},"route":"/targets/gpc3/","neighbours":{"cancer":[{"id":"hcc-advanced","kind":"cancer","name":"Advanced hepatocellular carcinoma (BCLC C)","route":"/cancers/hcc-advanced/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"}],"drug":[{"id":"azd9793","kind":"drug","name":"AZD9793","route":"/drugs/azd9793/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"pathway":[{"id":"hepatocellular-carcinoma-signalling","kind":"pathway","name":"Hepatocellular carcinoma (KEGG map)","route":"/pathways/hepatocellular-carcinoma-signalling/"},{"id":"proteoglycans-in-cancer","kind":"pathway","name":"Proteoglycans in cancer","route":"/pathways/proteoglycans-in-cancer/"},{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"roadmap":[{"id":"cell-therapy-roadmap","kind":"roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","route":"/roadmaps/cell-therapy-roadmap/"}],"idea":[{"id":"idea-in-vivo-car-solid","kind":"idea","name":"In vivo CAR-T against solid-tumour antigens","route":"/ideas/idea-in-vivo-car-solid/"}],"person":[{"id":"li-zonghai","kind":"person","name":"Zonghai Li","route":"/people/li-zonghai/"}],"institution":[{"id":"zhongshan-hospital-fudan","kind":"institution","name":"Zhongshan Hospital, Fudan University","route":"/institutions/zhongshan-hospital-fudan/"}]}}