Glypican-3 (GPC3)
Glypican-3 (GPC3) is a heparan sulfate proteoglycan tethered to the outer face of the plasma membrane by a glycosylphosphatidylinositol anchor.
Glypican-3 (GPC3) is a heparan sulfate proteoglycan tethered to the outer face of the plasma membrane by a glycosylphosphatidylinositol anchor. In development it modulates growth factor signaling at the cell surface — notably Wnt, Hedgehog and fibroblast growth factor pathways — and its loss-of-function causes Simpson-Golabi-Behmel syndrome, an X-linked overgrowth disorder, while its effects on growth-factor signaling depend on context. Its expression is oncofetal: abundant in fetal liver, silenced after birth, and re-expressed in tumors, where the same protein appears to switch to potentiating Wnt/β-catenin signaling.
That pattern is what makes it useful in hepatocellular carcinoma (HCC). GPC3 is expressed in most hepatocellular carcinomas and is absent from normal liver and from benign lesions such as regenerative nodules, so its detection by immunohistochemistry helps distinguish well-differentiated HCC from cirrhotic nodules and hepatocellular adenoma — a distinction that histology alone can leave unresolved. As a serum marker it complements rather than replaces α-fetoprotein: performance varies between studies and neither is specific to HCC on its own, while combining the two improves detection over either alone. Expression is not confined to liver tumors, appearing in melanoma, squamous lung carcinoma and germ cell tumors, so specificity holds against normal liver rather than against cancer in general.
Being a cell-surface antigen largely absent from healthy adult tissue, GPC3 is also a target rather than only a marker. chimeric antigen receptor T cells, bispecific antibodies, antibody-drug conjugates and peptide vaccines directed at it are in clinical development for HCC, alongside radiolabeled and fluorescent binders for imaging and intraoperative guidance — the same restricted expression serving diagnosis and therapy for the same reason.
Where the papers sit
13 papers from the last 6 months study Glypican-3 (GPC3) directly · updated from PubMed 8 Oct 2026
Study type 0 clinical trials · 1 human data · 11 preclinical · 1 unclassified
Themes 3 themes · 1 new direction
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GPC3-Directed Cellular Immunotherapy
GPC3-directed cellular immunotherapy is moving from standalone CAR designs toward engineered, locally delivered and combination approaches. Studies optimize CAR-T manufacturing, surface charge, fourth-generation signaling and hydrogel delivery to improve activity in hepatocellular carcinoma. Low antigen density and tumor heterogeneity recur as barriers, prompting cytokine optimization, CAR-NK combinations with enoblituzumab and bispecific T-cell engagers against EpCAM. The evidence is largely preclinical, leaving durability, safety and performance in heterogeneous solid tumors unresolved.
6 papers · 46.2%
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GPC3-Targeted Tumor Imaging
GPC3-targeted imaging is moving toward noninvasive localization and characterization of hepatocellular carcinoma. Albumin-binding and 18F- or 68Ga-labeled peptides are being evaluated with PET in GPC3-positive and GPC3-negative models. Membrane-engineered platforms extend detection to MRI and microhepatocellular carcinoma, while one multimodal nanoplatform links imaging with ferroptosis and photothermal therapy. Evidence remains primarily preclinical, with specificity and sensitivity still central questions.
4 papers · 30.8%
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Others — Nanoparticle Cancer Applications
Nanoparticle work in liver cancer spans GPC3 mRNA vaccines and lipid-based delivery, while a separate study develops a whole-blood nanoplasmonic biosensor. Vaccine strategies aim to generate antitumor immunity against hepatocellular carcinoma, with bivalent neoantigen formulations eradicating tumors in mice. AFP and proinflammatory cytokines recur as disease or immune-response markers. The mixed therapeutic and diagnostic focus does not establish one translational direction.
3 papers · 23.1%
GPC3 is used as a directly transduced analyte in an instrument-free whole-blood nanoplasmonic biosensor
The SiNP-chitosan nanocomposite biosensor for hepatocellular carcinoma uses anti-GPC3-functionalized gold nanoparticles embedded in hydrogel beads to convert GPC3 binding in unprocessed finger-prick blood into simultaneous colorimetric and LSPR signals, rather than treating GPC3 only as a tumor-localizing imaging target, vaccine antigen, or therapeutic target. This assigns GPC3 a distinct role as the directly measured analyte in an autonomous point-of-care diagnostic platform, enabling plasma separation and quantitative detection without laboratory instruments or sample processing 42233753Jun.
Papers
The 13 papers from the last 6 months that study Glypican-3 (GPC3) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
GPC3-Directed Cellular Immunotherapy (6)
- Manufacturing and electrostatic surface optimization of CAR-T cells improve therapeutic efficacy in liver malignancies. Hepatology communications · 1 Aug 2026 PMID 42538870
- CAR T cells secreting anti-EpCAM bispecific T cell engagers overcome tumor heterogeneity in targeting epithelial-originated carcinomas. Molecular therapy : the journal of the American Society of Gene Therapy · 21 Jul 2026 PMID 42478044
- Comparative in vitro evaluation of fourth-generation anti-GPC3 CAR T-cells in hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 6 Jul 2026 PMID 42407326
- Large language model-guided CAR-T in silico platform for cytokine optimization in liver cancer with low antigen density. Journal of hematology & oncology · 2 Jul 2026 PMID 42387611
- GPC3 chimeric antigen receptor (CAR)-NK cells combined with Enoblituzumab enhance the anti-tumor efficacy against hepatocellular carcinoma. Biochemical and biophysical research communications · 30 Jun 2026 PMID 42378857
- Local delivery of GPC3-CAR T cells in a thermosensitive hydrogel enhances antitumor efficacy in hepatocellular carcinoma. International immunopharmacology · 6 Jun 2026 PMID 42250289
GPC3-Targeted Tumor Imaging (4)
- Development and Evaluation of an Albumin-Binding GPC3-Targeting Peptide for PET Imaging of Hepatocellular Carcinoma. Molecular pharmaceutics · 8 Jun 2026 PMID 42258609
- In vivo membrane engineering traps Gd-based MRI contrast agents for detecting microhepatocellular carcinoma. Science advances · 29 Apr 2026 PMID 42054448
- Synthesis and Preclinical Evaluation of [18F]AlF-NOTA-A2P-GPC3P for Imaging of GPC3. Molecular pharmaceutics · 27 Apr 2026 PMID 42037560
- Genetically Engineered Membrane-Mimetic Liposome-Wrapped Violet Phosphorus Nanoplatform for Targeted Synergistic Ferroptosis/Photothermal/Immunotherapy of Hepatocellular Carcinoma. ACS applied materials & interfaces · 24 Apr 2026 PMID 42027106
Others — Nanoparticle Cancer Applications (3)
- A novel bivalent neoantigen vaccine based on mRNA-loaded lipid nanoparticles eradicates hepatocellular carcinoma in mice. Journal of controlled release : official journal of the Controlled Release Society · 13 Jul 2026 PMID 42442546
- A SiNP-Chitosan Nanocomposite Converts Hydrophobic 3D-Printed Microchannels into Whole-Blood-Operable Nanoplasmonic Biosensors. ACS biomaterials science & engineering · 3 Jun 2026 PMID 42233753
- Dual-adjuvanted GPC3 mRNA vaccine delivered by lipid nanoparticles for hepatocellular carcinoma immunotherapy. Journal of controlled release : official journal of the Controlled Release Society · 11 May 2026 PMID 42114776
By study type
Human data, design not indexed (1)
- Comparative in vitro evaluation of fourth-generation anti-GPC3 CAR T-cells in hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 6 Jul 2026 PMID 42407326
Preclinical: animal, cell and lab studies (11)
- Manufacturing and electrostatic surface optimization of CAR-T cells improve therapeutic efficacy in liver malignancies. Hepatology communications · 1 Aug 2026 PMID 42538870
- CAR T cells secreting anti-EpCAM bispecific T cell engagers overcome tumor heterogeneity in targeting epithelial-originated carcinomas. Molecular therapy : the journal of the American Society of Gene Therapy · 21 Jul 2026 PMID 42478044
- Large language model-guided CAR-T in silico platform for cytokine optimization in liver cancer with low antigen density. Journal of hematology & oncology · 2 Jul 2026 PMID 42387611
- GPC3 chimeric antigen receptor (CAR)-NK cells combined with Enoblituzumab enhance the anti-tumor efficacy against hepatocellular carcinoma. Biochemical and biophysical research communications · 30 Jun 2026 PMID 42378857
- Development and Evaluation of an Albumin-Binding GPC3-Targeting Peptide for PET Imaging of Hepatocellular Carcinoma. Molecular pharmaceutics · 8 Jun 2026 PMID 42258609
- Local delivery of GPC3-CAR T cells in a thermosensitive hydrogel enhances antitumor efficacy in hepatocellular carcinoma. International immunopharmacology · 6 Jun 2026 PMID 42250289
- A SiNP-Chitosan Nanocomposite Converts Hydrophobic 3D-Printed Microchannels into Whole-Blood-Operable Nanoplasmonic Biosensors. ACS biomaterials science & engineering · 3 Jun 2026 PMID 42233753
- Dual-adjuvanted GPC3 mRNA vaccine delivered by lipid nanoparticles for hepatocellular carcinoma immunotherapy. Journal of controlled release : official journal of the Controlled Release Society · 11 May 2026 PMID 42114776
- In vivo membrane engineering traps Gd-based MRI contrast agents for detecting microhepatocellular carcinoma. Science advances · 29 Apr 2026 PMID 42054448
- Synthesis and Preclinical Evaluation of [18F]AlF-NOTA-A2P-GPC3P for Imaging of GPC3. Molecular pharmaceutics · 27 Apr 2026 PMID 42037560
- Genetically Engineered Membrane-Mimetic Liposome-Wrapped Violet Phosphorus Nanoplatform for Targeted Synergistic Ferroptosis/Photothermal/Immunotherapy of Hepatocellular Carcinoma. ACS applied materials & interfaces · 24 Apr 2026 PMID 42027106
Unclassified: not yet indexed with MeSH (1)
- A novel bivalent neoantigen vaccine based on mRNA-loaded lipid nanoparticles eradicates hepatocellular carcinoma in mice. Journal of controlled release : official journal of the Controlled Release Society · 13 Jul 2026 PMID 42442546
Written from 13 PubMed abstracts, each one listed by PMID above. Published: 2026-07-14. Last written: 2026-08-26 by GPT. Corrections: 2026-09-26 by GPT. Drafted by language models from published abstracts; not medical advice.