GPC3 expression

This study uncovered TiME heterogeneity among GC patients with different MMR states, highlighting that the pMMR TiME is distinguished by hypoxia, pro-angiogenesis, and ECM remodeling, driven by the presence of GC2 cells, SPP1 + macrophages, FAP + fibroblasts, and E2 endothelial cells. These findings are pivotal for developing targeted immunotherapies for GC patients with pMMR.

GPC-3's re-expression in HCC and its involvement in key tumorigenic processes underscore its value as a biomarker for early diagnosis and a target for therapeutic intervention. Further research is warranted to fully exploit GPC-3's diagnostic and therapeutic potential in HCC management.

Ki-67 IHC as a proliferation marker, particularly when assessed via automated methods, was helpful in distinguishing AC from AB cases. In contrast to other studies, surrogate IHC markers of embryonic stem cells, SOX2, OCT4 and GPC-3, were unreliable in distinguishing the two entities.

These macrophages carry a cargo of the TLR7/TLR8 agonist R848 and INCB024360, a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, wrapped in C16-ceramide-fused outer membrane vesicles (OMV) of Escherichia coli origin (RILO)...RILO-loaded macrophages exert therapeutic efficacy in mice bearing H22 hepatocellular carcinomas, which express high levels of glypican-3. Overall, we lay down the proof of principle for a cytotherapeutic strategy to target solid tumours and could complement conventional treatment.

GPC3-specific optical imaging enabled the detection of the GPC3+ HCC cells and noninvasive monitoring of tumor response to adoptive immunotherapy. The integrated development of a targeted therapeutic and molecular imaging probe provides a novel paradigm for developing cancer theranostics.

INI1 loss was not associated with yolk sac morphology or immunomarker expression in the endometrium, and BRG1 loss was rare. All patients with MMR-deficient carcinomas with yolk sac immunoexpression +/- morphology were disease-free on follow-up, whereas the majority of MMR-intact cancers showed aggressive disease.

Furthermore, the tumor-to-organ ratios of [18F]AlF-NOTA-IPB-GPC3P surpassed those of [18F]AlF-GP2633. Our results support the utilization of [18F]AlF-NOTA-IPB-GPC3P as a PET imaging agent targeting the GPC3 receptor for tumor detection.

P2, N=30, Recruiting, Eureka Therapeutics Inc. | Trial completion date: Dec 2027 --> Dec 2026

Collectively, our findings shed light on the molecular mechanisms through which Rh2 modulates HCC growth, which involve the regulation of angiogenesis and the glypican-3/Wnt/β-catenin pathway. These insights may pave the way for the development of novel therapeutic strategies targeting these pathways for the treatment of HCC.

P2, N=24, Recruiting, Eureka Therapeutics Inc. | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

P2, N=24, Recruiting, Eureka Therapeutics Inc. | Phase classification: P1/2 --> P2

A combined model including AP Rad-score and serum AFP levels based on contrast-enhanced CT could preoperatively predict GPC3-positive expression in HCC.

The results show that circulating extracellular vesicle GPC3 (eGPC3) levels are a reliable marker for GPC3 expression in tumor, opening up new avenues for tumor diagnosis. We created an eGPC3 assay based on the CRISPR-Cas13a system, and successfully study the significance of extracellular vesicle GPC3 markers in hepatocellular carcinoma.

FFPE slides were stained for GPC3+ (GC33, Ventana), PD-L1+ (22C3, Dako) cells and then scanned at 20x using the Aperio Versa8 scanner... Here we profiled GPC3 expression across tumor types and showed high level of expression in HCC followed by SQ-NSCLC. We have established an AI-powered digital pathology platform that can provide a standardized, scalable, and reproducible method of characterizing GPC3 positivity to support further patient selection in clinical study.

Therapeutically, significant and durable tumor regression and survival benefit were achieved with 177Lu- and 225Ac-labeled RAYZ-8009, as single agents and in combination with lenvatinib, in GPC3-positive HCC xenografts. Preclinical in vitro and in vivo data demonstrate the potential of RAYZ-8009 as a theranostic agent for the treatment of patients with GPC3-positive HCC.

P1, N=48, Recruiting, Zhejiang University | N=20 --> 48

Our study confirmed that PSMA-positive TAV is a prospective diagnostic and prognostic biomarker for HCC. Co-expression of PSMA with PD-L1 may suggest potential crosstalk between the 2 proteins, likely regulating the tumor microenvironment.

P1/2, N=110, Recruiting, Sotio Biotech Inc. | Trial completion date: Jul 2039 --> Dec 2041 | Trial primary completion date: Jul 2024 --> Apr 2026

Postoperative adjuvant chemotherapy was given to three patients. AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.

P1/2, N=24, Recruiting, Eureka Therapeutics Inc. | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024 | N=12 --> 24

P1, N=11, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting | N=18 --> 11

Hypoxia promoted secretion of exosomal GPC3 through the activation of HIF-1α. GPC3-deficient exosomes inhibited the proliferation, migration and EMT of HCC cells via the Wnt/β-catenin signaling pathway, and suppressed the angiogenic potential of HUVECs. This provided a novel understanding of the role of exosomal GPC3 in HCC progression.

P1/2, N=106, Recruiting, Sanofi | Trial completion date: May 2030 --> Dec 2030 | Trial primary completion date: May 2030 --> Dec 2030

P=N/A, N=8, Not yet recruiting, the Affiliated Drum Tower Hospital, Medical School of Nanjing University; Nanjing Zilong Biotechnology Co., LTD | .

The nomogram combining multiparametric MRI and clinical indicators is found to have satisfactory predictive efficacy for preoperative prediction of GPC3-positive HCC. Accordingly, the proposed method can promote individualized risk stratification and further treatment decisions of HCC patients.

These data indicated that GPC3 peptide-specific CD8 T cells had potent antitumor activity against TYST tumor, particularly for combined treatment with the peptide, which was partially dependent on the intratumoral cGAS/STNG signaling. GPC3 peptide vaccine may be valuable for the combination treatment of TYST.

Three HLA-A2-restricted GPC3 antigenic peptides were synthesized, with GPC3 FLAELAYDL and GPC3 FLIIQNAAV antigenic peptide-modified DCs inducing CTL production, and exhibiting strong targeted killing ability in LUSC cells at 80 : 1 multiplicity of infection. GPC3 may advance the onset and progression of LUSC, and GPC3 FLAELAYDL and GPC3 FLIIQNAAV antigenic peptide-loaded DC-induced CTLs have a superior killing ability against LUSC cells.

Finally, we identified 3 potential inhibitors of GPC3 in human LUAD, namely heparitin, gemcitabine and arbutin. In conclusion, GPC3 may play an important role in the development of LUAD and could serve as a promising biomarker in LUAD.

It was validated that GLS1 was a sensitive and specific biomarker for pathological diagnosis of HCC and had prognostic value, thus having practical value for clinical application.

Combined DWI and F-FDG PET/CT is superior to a single technique in evaluating the expression of GPC-3 in HCC patients. However, the combined model did not benefit the Ki-67 group.

miR-96-5p participates in the development of papillary thyroid cancer by regulating the expression of GPC3. Thus, targeting miR-96-5p may be a potential therapeutic approach for preventing and treating papillary thyroid cancer.

No abstract available

Herein, we have reviewed the role of microRNAs in regulating cancer cells' response to oxaliplatin, with particular attention to gastrointestinal cancers. We also discussed the role of these noncoding RNAs in the pathophysiology of oxaliplatin-induced neuropathic pain.

DCA also showed that the nomogram had the highest net clinical benefit for predicting GPC3 expression.In the validation cohort, the ROC curve results showed predicted GPC3-positive expression nomogram model AUC, sensitivity, and specificity of 0.800, 58.5%, and 100.0%, respectively. HBP radiomics features are closely associated with GPC3-positive expression, and combined clinicoradiologic factors and radiomics features nomogram may provide an effective way to non-invasively and individually screen patients with GPC3-positive HCC.

GPC3 protein is expressed in a large percentage of HB and FLC tumors, but with variable intensity and distribution. Characterization of GPC3 tumor protein H-score and pattern of immunoreactivity are two independent parameters that may be helpful to quantitate GPC3 immunostaining of tumor and correlate with treatment response to a variety of GPC3 targeted therapeutics.

FZD7 and GPC3 gene expressions have a complementary role in early HCC detection, with a greater diagnostic sensitivity and accuracy than AFP. In addition, FZD7 rs2280509 polymorphism is significantly associated with an increased risk of HCC in the Egyptian population.

Knockout lines of HepG2 and Hep3B exhibited decreased cell proliferation, migration, and in vivo tumor growth compared to wildtype. GPC-3 deficiency was associated with increased sensitivity to radiation therapy. Studies identifying the pathways through which this radiosensitivity is mediated are ongoing.

Importantly, STK-009 induced the expression of cytotoxic machinery, pro-survival, and proliferative genes in tumor-infiltrating SYNCAR-002 (figure 3). Conclusions These findings validate that the orthogonal IL-2 platform has the potential to improve the efficacy and durability of CAR T therapy for solid tumor targets such as GPC3 by selectively expanding CAR-T cells in vivo and activating CAR-T cells in a hostile tumor microenvironment.

GC33, a humanized mAb directed against GPC3, is a safe and well-tolerated therapy choice for patients with HCC, which tested in a phase I trial in advanced HCC patients...CD16A activation and increased cytokines release were associated with higher anti-tumor activity. In conclusion, this bispecific antibody may possibly help develop new therapeutic strategies for HCC and develop new treatment options in the future.