Affinage

CLDN18

Claudin-18 · UniProt P56856

Length
261 aa
Mass
27.9 kDa
Annotated
2026-06-09
91 papers in source corpus 17 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLDN18 encodes a tight junction structural protein expressed as two tissue-restricted isoforms whose function and oncogenic relevance diverge sharply between lung and gastric/pancreatic tissue (PMID:26146084, PMID:30325015). In lung adenocarcinoma, the lung-specific isoform CLDN18.1 acts as a tumor suppressor, inhibiting IGF-1R and AKT phosphorylation and reducing the YAP/TAZ transcriptional co-activators and their target genes (PMID:30325015). In the stomach, a chromosomal rearrangement fusing CLDN18 to ARHGAP26 produces a gain-of-function oncoprotein that disrupts epithelial integrity, causes EMT-like morphology, impaired barrier and adhesion, and increased invasion (PMID:26146084), and in vivo drives diffuse gastric cancer by activating RHOA, FAK and YAP signaling and inducing signet ring cell formation, cooperating with Trp53 loss (PMID:38621923). The gastric isoform CLDN18.2 is a major immunotherapy target: normally concealed within tight junctions, it becomes surface-exposed upon malignant transformation and loss of polarity (PMID:41521591, PMID:33610734), enabling antibodies such as zolbetuximab to kill tumor cells via NK-cell ADCC and complement-dependent cytotoxicity (PMID:41521591, PMID:36922936), and supporting antibody-drug conjugates that internalize to lysosomes to release cytotoxic payloads (PMID:37788341, PMID:39227365). CLDN18.2 trafficking and signaling are further controlled post-translationally: O-GlcNAcylation at T204, driven by KRAS mutation and hyperglycemia, drives cytoplasmic mislocalization, reduces PTP1B binding, and recruits Src to promote pancreatic cancer progression and therapy resistance (PMID:41513443). CLDN18.2 can also be transferred to CD8+ T cells via trogocytosis, where it binds β-catenin through its C-terminal domain to promote GSK3β/CK1α-mediated β-catenin degradation, suppressing T-cell glycolysis and cytotoxicity (PMID:41667243).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2003 Medium

    Established the therapeutic principle that surface CLDN18.2 can be exploited for immune-mediated tumor killing, defining the mechanism of anti-CLDN18.2 antibodies.

    Evidence ADCC and CDC assays with NK cell depletion plus clinical pharmacodynamic confirmation for zolbetuximab

    PMID:41521591

    Open questions at the time
    • Review synthesis rather than single primary dataset
    • Does not define the molecular determinants of antigen surface exposure
  2. 2015 High

    Resolved how the CLDN18-ARHGAP26 fusion alters cell behavior, showing it abolishes epithelial barrier/adhesion and confers invasion.

    Evidence Whole-genome paired-end sequencing for fusion discovery; barrier, adhesion, wound-healing, RHOA, and invasion assays in epithelial cell lines

    PMID:26146084

    Open questions at the time
    • Initial model attributed phenotype to RHOA inhibition, later contradicted
    • Cell-line overexpression rather than physiologic context
  3. 2018 High

    Defined CLDN18.1 as a lung tumor suppressor acting through IGF-1R/AKT and YAP/TAZ, distinguishing isoform-specific function.

    Evidence Cldn18-/- mice, rescue in LuAd cell lines, Western blot, siRNA epistasis, xenografts

    PMID:30325015

    Open questions at the time
    • Direct biochemical link between CLDN18.1 and IGF-1R not established
    • Mechanism of YAP/TAZ suppression unclear
  4. 2023 Medium

    Identified upstream control of CLDN18 by miR-448 and linked CLDN18.2 to YAP phosphorylation/cytoplasmic retention in gastric cancer.

    Evidence Luciferase 3'-UTR reporter, Co-IP, cytoplasmic-nuclear fractionation, in vitro and xenograft assays

    PMID:37023839

    Open questions at the time
    • Mechanism of YAP Ser127 phosphorylation by CLDN18.2 not defined
    • Single lab
  5. 2024 High

    Overturned the original RHOA-inhibition model, showing the fusion is a gain-of-function oncogene activating RHOA, FAK, and YAP in vivo.

    Evidence Transgenic LSL-CLDN18-ARHGAP26 knock-in mice and gastric organoids; RHOA/FAK/YAP biochemistry; FAK/YAP-TEAD inhibitor epistasis

    PMID:38621923

    Open questions at the time
    • Molecular basis for RHOA activation by a GAP-domain-containing fusion unresolved
    • Relationship to ARHGAP26 catalytic activity unclear
  6. 2024 Medium

    Connected the fusion to an immunosuppressive microenvironment via PI3K/AKT-mTOR-FAS lipid metabolism favoring Tregs.

    Evidence Coculture and xenograft models with PI3K inhibitor and free-fatty-acid measurement

    PMID:39164472

    Open questions at the time
    • Direct CLDN18-fusion-to-PI3K mechanistic link not detailed
    • Single lab
  7. 2024 Medium

    Characterized ADC mechanism of action, showing payload-induced apoptosis is opposed by cytoprotective autophagy via Akt/mTOR inactivation.

    Evidence Caspase-9/PARP cleavage, LC3 flux, Akt/mTOR analysis, autophagy inhibitor combination, xenografts

    PMID:39227365

    Open questions at the time
    • Generality across ADC formats unknown
    • Single lab
  8. 2024 High

    Identified O-GlcNAcylation at T204 as a metabolic switch controlling CLDN18.2 localization, PTP1B/Src signaling, and therapy resistance.

    Evidence Site-specific T204A mutagenesis, KPC/PDX/organoid models, IP, fractionation, Src/PTP1B kinase assays, KRAS inhibitor combination

    PMID:41513443

    Open questions at the time
    • Enzyme catalyzing T204 O-GlcNAcylation not identified
    • Whether modification occurs in gastric versus pancreatic disease unaddressed
  9. 2024 Medium

    Defined Fc-mediated CLDN18.2/CD3 BiTE engagement of CD64+ CAFs as a driver of desmoplasia limiting T-cell infiltration.

    Evidence Fibroblast Fcgr1 KO mice, molecular docking, ChIP, VAV2 phosphorylation assay, vilanterol rescue in PDAC models

    PMID:39187291

    Open questions at the time
    • Concerns the antibody Fc, not CLDN18 protein function directly
    • Single lab
  10. 2024 Medium

    Identified LINC01547-ORF as a CLDN18-binding micropeptide that stabilizes CLDN18 and suppresses FAK/PI3K/AKT in colorectal cancer.

    Evidence Co-IP, immunofluorescence colocalization, ubiquitination assay, Western blot, docking

    PMID:39659940

    Open questions at the time
    • Single Co-IP-based interaction without reciprocal in vivo validation
    • Isoform specificity not resolved
  11. 2025 Medium

    Demonstrated that surface exposure of CLDN18.2 upon loss of polarity is the mechanistic basis for selective antibody targeting.

    Evidence Synthesis of preclinical pharmacodynamic and translational evidence

    PMID:33610734 PMID:41521591

    Open questions at the time
    • Review-level synthesis, not a single primary dataset
    • Quantitative epitope accessibility not measured
  12. 2025 Medium

    Revealed a role for Cldn18 loss in promoting less-fibrogenic alveolar transitional progenitors and protection from lung fibrosis.

    Evidence Cldn18 KO mice, bleomycin model, lineage tracing, single-nucleus multiome (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Direct molecular role of CLDN18 in AT2-to-AT1 differentiation undefined
  13. 2026 High

    Uncovered trogocytic transfer of CLDN18.2 to CD8+ T cells as an immune-evasion mechanism via β-catenin degradation and metabolic suppression.

    Evidence Humanized/KPC/KO/PDX models, IP-MS, domain mapping, glycolysis and ubiquitination assays, peptide (PC18.1) rescue

    PMID:41667243

    Open questions at the time
    • Frequency and clinical relevance of trogocytosis in patients unquantified
    • Whether antibody therapy alters trogocytic transfer unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the two isoforms' shared tight-junction structural role mechanistically connects their opposing tumor-suppressive (lung) versus oncogenic-target (gastric/pancreatic) behaviors remains unresolved.
  • No unifying structural model linking junction function to signaling outputs
  • Isoform-specific interactomes incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0098631 cell adhesion mediator activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-1500931 Cell-Cell communication 1
Partners
ARHGAP26CK1ΑCTNNB1LINC01547-ORFPTP1BSRC
Complex memberships
tight junction

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 The CLDN18-ARHGAP26 fusion protein (resulting from chromosomal rearrangement fusing the tight junction gene CLDN18 with the RHOA inhibitor-encoding ARHGAP26) induces loss of epithelial integrity: epithelial cell lines expressing the fusion showed dramatic EMT-like morphology with long protrusions, impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, inhibition of RHOA activity, and gain of invasion in cancer cell lines. DNA paired-end-tag whole-genome sequencing to identify fusions; expression of fusion in epithelial cell lines; barrier function assays; adhesion assays; wound healing assays; RhoA activity measurement; invasion assays Cell reports High 26146084
2024 The CLDN18-ARHGAP26 fusion protein is a gain-of-function oncogene in diffuse gastric cancer: contrary to the initial model that it inhibits RHOA (via ARHGAP26 GAP activity), expression of the fusion in gastric organoids promoted activation of RHOA and downstream effector signaling, activated focal adhesion kinase (FAK), and induced YAP pathway activation. The fusion induced signet ring cell formation and cooperatively transformed gastric cells when combined with Trp53 loss. Transgenic mouse model (LSL-CLDN18-ARHGAP26 knock-in); gastric organoids derived from the model; biochemical assays of RHOA activity and downstream signaling; FAK and YAP pathway analysis; FAK/YAP-TEAD inhibitor combination studies; tumor growth assays Gut High 38621923
2018 CLDN18.1, the lung-specific isoform of CLDN18, inhibits IGF-1R and AKT phosphorylation and decreases expression of transcriptional co-activators TAZ and YAP (and their target genes) in lung adenocarcinoma cells, contributing to tumor suppressor activity. Silencing of TAZ (and possibly YAP) with siRNA also implicated TAZ in CLDN18.1-mediated AKT inactivation. Restoration of CLDN18.1 expression in LuAd cell lines; Western blot analysis of IGF-1R and AKT phosphorylation; siRNA knockdown of YAP and TAZ; xenograft tumor growth assays; Cldn18-/- mouse lung alveolar epithelial type II cell high-throughput analysis; cell proliferation, migration, invasion, and colony formation assays International journal of cancer High 30325015
2024 CLDN18-ARHGAP fusion-positive gastric cancer cells activate PI3K/AKT-mTOR-FAS signaling, which enhances free fatty acid production to favor the survival of regulatory T (Treg) cells, contributing to an immunosuppressive tumor microenvironment. PI3K inhibition reversed Treg upregulation and enhanced anti-tumor cytotoxicity of neoantigen-reactive T cells. In vitro coculture models; xenograft gastric cancer models; PI3K inhibitor treatment; measurement of free fatty acid production; Treg cell survival and frequency assays EMBO molecular medicine Medium 39164472
2020 CLDN18.1 expression is inversely regulated by promoter methylation in lung adenocarcinoma, and its restoration suppresses malignant properties (proliferation, migration, invasion, anchorage-independent growth) and inhibits IGF-1R and AKT phosphorylation, as well as reducing TAZ and YAP expression. Promoter methylation analysis; restoration of CLDN18.1 in LuAd cells; Western blot; in vitro functional assays (proliferation, migration, invasion); xenograft models (referenced in context of CLDN18.1 study) Aging Low 32668412
2023 miR-448 directly targets the 3'-UTR of CLDN18 and represses its expression in gastric cancer cells; CLDN18.2 overexpression suppresses YAP/TAZ transcriptional co-activator activity and promotes cytoplasmic retention of phosphorylated YAP (at Ser-127), thereby inhibiting GC cell proliferation and metastasis. Luciferase reporter assay with CLDN18 3'-UTR; RNA-seq; qRT-PCR; Co-IP; cytoplasmic-nuclear fractionation; Western blot; in vitro proliferation and metastasis assays; in vivo xenograft Journal of ethnopharmacology Medium 37023839
2003 Zolbetuximab (anti-CLDN18.2 monoclonal antibody) mediates killing of CLDN18.2-positive tumor cells through immune effector mechanisms including antibody-dependent cellular cytotoxicity (ADCC) via NK cells and complement-dependent cytotoxicity (CDC). This mechanism requires high antigen density on the cell surface and is enhanced by chemotherapy-induced CLDN18.2 upregulation. Preclinical pharmacodynamic studies; ADCC and CDC assays; NK cell depletion experiments; phase I pharmacodynamic assessment confirming NK/complement engagement in patients Expert review of anticancer therapy Medium 41521591
2022 ZL-1211, an anti-CLDN18.2 antibody engineered for enhanced ADCC, induces NK cell-dependent tumor cell killing; NK cell depletion abrogated ZL-1211-mediated ADCC in vitro, and in vivo efficacy was also dependent on the presence of an NK compartment. ZL-1211 triggered NK cell activation with robust inflammatory cytokine production (IFNγ, TNFα, IL6) and NK cell recruitment into the tumor microenvironment. NK cell depletion in vitro ADCC assays; mouse xenograft models with NK depletion; cytokine measurement; patient-derived gastric tumor coculture; in vivo tumor models Cancer research communications Medium 36922936
2024 CLDN18.2-directed ADC (αCLDN18.2-MMAE) induces dose-dependent apoptosis via caspase-9/PARP cleavage in CLDN18.2-positive gastric cancer cells; treatment also activates cytoprotective autophagy (evidenced by autophagosome accumulation, LC3-I to LC3-II conversion, complete autophagic flux) via Akt/mTOR pathway inactivation. Inhibiting autophagy enhances ADC-induced cytotoxicity and apoptosis. In vitro cytotoxicity assays; Western blot for caspase-9/PARP cleavage; LC3 conversion assay; autophagic flux measurement; Akt/mTOR phosphorylation analysis; autophagy inhibitor (LY294002) combination; in vivo xenograft tumor models Cell death discovery Medium 39227365
2024 CLDN18.2 undergoes O-GlcNAcylation at threonine-204 (T204), driven cooperatively by KRAS mutation and hyperglycemia. This O-GlcNAcylation promotes cytoplasmic accumulation of CLDN18.2 (rather than membrane localization), enhances pancreatic cancer migration, invasion, and metastasis, and reduces sensitivity to anti-CLDN18.2 targeted therapy. Mechanistically, O-GlcNAcylated CLDN18.2 shows reduced binding to PTP1B, leading to enhanced tyrosine phosphorylation; it also recruits Src via its SH2 domain to trigger Src activation. Genetic (T204A mutation) or pharmacological blockade of O-GlcNAcylation restores membrane localization and suppresses tumor progression. Patient-derived xenograft and organoid models; KPC mice; KPC-Cldn18.2 KO mice; site-specific mutagenesis (T204A); immunoprecipitation; subcellular fractionation; kinase activity assays (Src, PTP1B); KRASG12D inhibitor (MRTX1133) combination studies; migration/invasion assays Gut High 41513443
2026 CD8+ T cells acquire CLDN18.2 from tumor cells via trogocytosis; 'dressed' CLDN18.2 on CD8+ T cells suppresses glucose uptake and glycolysis in those T cells, impairing their cytotoxicity. Mechanistically, trogocytosis-related CLDN18.2 induces GSK3β/CK1α-mediated β-catenin phosphorylation, promoting β-catenin ubiquitination and proteasomal degradation. CLDN18.2 interacts with β-catenin's N-terminal domain via its own C-terminal domain, strengthening the β-catenin/CK1α interaction. CLDN18.2+CD8+ T cells home to bone marrow via CXCL12/CXCR4, skew HSC myeloid differentiation, and induce systemic immune senescence via IL1α. Humanized hCD34+, KPC, Cldn18.2 KO, and PDX/organoid mouse models; flow cytometry; immunofluorescence; single-cell RNA-sequencing; immunoprecipitation-mass spectrometry (IP-MS); peptide (PC18.1) disrupting CLDN18.2/β-catenin interaction; glycolysis assays; ubiquitination assays Gut High 41667243
2024 CLDN18.2 antibody-drug conjugate (CLDN18.2-307-ADC) binds the extracellular domain of CLDN18.2, is internalized upon binding, and subsequently localizes to the lysosomal compartment, where the MMAE payload is released to induce complete and sustained tumor regression. The parental mAb (CLDN18.2-307) induces ADCC against CLDN18.2-positive cells. Antibody-CLDN18.2 binding assays; internalization and lysosomal co-localization assays; ADCC assays; CDX and PDX xenograft models Molecular cancer therapeutics Medium 37788341
2025 CLDN18.2 is normally concealed within tight junctions in healthy gastric mucosa; upon malignant transformation and loss of cell polarity, CLDN18.2 epitopes become exposed on the tumor cell surface, making it accessible to antibody targeting. This exposure is the mechanistic basis for selective antibody-dependent cytotoxicity by zolbetuximab. Referenced from preclinical pharmacodynamic studies and review of translational evidence; not a single primary experimental paper but synthesis of mechanistic evidence Expert review of anticancer therapy Medium 33610734 41521591
2024 The Fc fragment of CLDN18.2/CD3 BiTE antibodies interacts with CD64+ cancer-associated fibroblasts (CAFs) via activation of the SYK-VAV2-RhoA-ROCK-MLC2-MRTF-A-α-SMA/collagen-I signaling pathway, enhancing desmoplasia and limiting late-stage T cell infiltration. Vilanterol suppressed BiTE-induced phosphorylation of VAV2 (Y172) in CD64+ CAFs, weakening desmoplasia. Fibroblast-specific Fcgr1 KO mice; flow cytometry; Masson staining; molecular docking; chromatin immunoprecipitation; VAV2 phosphorylation assay; in vivo PDAC models with vilanterol treatment Gut Medium 39187291
2025 Loss of Cldn18 in mouse lungs leads to the emergence of a distinct population of transitional alveolar progenitors (regeneration-associated transitional progenitors, RATPs), which are epigenetically distinct from damage-associated transitional progenitors (DATPs) and are less fibrogenic. Cldn18 KO mice are protected from bleomycin-induced fibrosis, with accelerated AT2-to-AT1 differentiation as the proposed mechanism. NKX2.1 and AP-1 are active in early transitions and TEAD factors in later stages during AT2-to-AT1 differentiation. Cldn18 KO mouse model; bleomycin fibrosis model; lineage tracing; single-nucleus multiome (RNA + ATAC); transcriptomic and epigenomic characterization of transitional progenitor populations bioRxivpreprint Medium
2024 LINC01547-ORF (a small protein encoded by lncRNA LINC01547) interacts physically with CLDN18 protein in colorectal cancer cells (demonstrated by Co-IP and immunofluorescence), reducing CLDN18 ubiquitination and promoting its protein expression. LINC01547-ORF targets CLDN18 to inhibit the FAK/PI3K/AKT signaling pathway, suppressing CRC cell proliferation and migration. Co-immunoprecipitation; immunofluorescence co-localization; ubiquitination assay; Western blot for FAK/PI3K/AKT; protein molecular docking; cell proliferation and migration assays American journal of cancer research Medium 39659940
2020 IL-1β downregulates claudin-18 expression to promote lung barrier function damage by signaling through the IL-1β-HER2/HER3 axis, contributing to ARDS pathogenesis. This was validated in cell experiments and animal models. Bioinformatics analysis; cell experiments with IL-1β stimulation and measurement of claudin-18 expression; lung barrier function assays; animal ARDS models Aging Low 32065780
2025 SUSD2 exerts tumor-suppressive effects in lung adenocarcinoma through regulation of the cell adhesion molecules pathway via modulation of CLDN18.2, thereby influencing cell adhesion dynamics. Chronic nanoplastic exposure downregulated SUSD2, leading to dysregulation of the SUSD2-CLDN18.2 signaling axis and enhanced malignant phenotypes. Chronic PS-NP exposure model (A549 cells, 6 months); SUSD2 overexpression rescue experiments; multi-omics analysis; cell adhesion and migration assays Ecotoxicology and environmental safety Low 40882394

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet (London, England) 610 37068504
2023 Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nature medicine 474 37524953
2021 FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Annals of oncology : official journal of the European Society for Medical Oncology 303 33610734
2015 Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity. Cell reports 120 26146084
2022 Multiplex immunohistochemistry defines the tumor immune microenvironment and immunotherapeutic outcome in CLDN18.2-positive gastric cancer. BMC medicine 92 35811317
2023 Targeting CLDN18.2 in cancers of the gastrointestinal tract: New drugs and new indications. Frontiers in oncology 66 36969060
2019 Targeting CLDN18.2 by CD3 Bispecific and ADC Modalities for the Treatments of Gastric and Pancreatic Cancer. Scientific reports 61 31182754
2019 Enrichment of CLDN18-ARHGAP fusion gene in gastric cancers in young adults. Cancer science 59 30771244
2018 Frequent CLDN18-ARHGAP fusion in highly metastatic diffuse-type gastric cancer with relatively early onset. Oncotarget 49 30034621
2020 The Significance of the CLDN18-ARHGAP Fusion Gene in Gastric Cancer: A Systematic Review and Meta-Analysis. Frontiers in oncology 40 32983960
2023 CLDN18.2 and 4-1BB bispecific antibody givastomig exerts antitumor activity through CLDN18.2-expressing tumor-directed T-cell activation. Journal for immunotherapy of cancer 39 37364935
2023 Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors. Journal of pharmaceutical analysis 34 37181294
2018 CLDN18.1 attenuates malignancy and related signaling pathways of lung adenocarcinoma in vivo and in vitro. International journal of cancer 33 30325015
2020 Analysis of the expression and genetic alteration of CLDN18 in gastric cancer. Aging 32 32668412
2022 Development and comparison of three 89Zr-labeled anti-CLDN18.2 antibodies to noninvasively evaluate CLDN18.2 expression in gastric cancer: a preclinical study. European journal of nuclear medicine and molecular imaging 30 35347439
2024 Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 29 39321207
2016 Coupling CDH17 and CLDN18 markers for comprehensive membrane-targeted detection of human gastric cancer. Oncotarget 28 27580354
2023 First-in-human CLDN18.2 functional diagnostic pet imaging of digestive system neoplasms enables whole-body target mapping and lesion detection. European journal of nuclear medicine and molecular imaging 27 37099132
2022 Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma. Cancer science 26 36478334
2020 Clinical Significance of CLDN18.2 Expression in Metastatic Diffuse-Type Gastric Cancer. Journal of gastric cancer 26 33425442
2024 Recurrent RhoGAP gene fusion CLDN18-ARHGAP26 promotes RHOA activation and focal adhesion kinase and YAP-TEAD signalling in diffuse gastric cancer. Gut 25 38621923
2020 Ultrasensitive Gastric Cancer Circulating Tumor Cellular CLDN18.2 RNA Detection Based on a Molecular Beacon. Analytical chemistry 25 33314914
2017 miR-767-3p Inhibits Growth and Migration of Lung Adenocarcinoma Cells by Regulating CLDN18. Oncology research 25 29169410
2025 CLDN18.2-targeting antibody-drug conjugate IBI343 in advanced gastric or gastroesophageal junction adenocarcinoma: a phase 1 trial. Nature medicine 24 40670773
2024 Health-related quality of life in patients with CLDN18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: results from the SPOTLIGHT and GLOW clinical trials. ESMO open 24 39146670
2023 CLDN18.2 BiTE Engages Effector and Regulatory T Cells for Antitumor Immune Response in Preclinical Models of Pancreatic Cancer. Gastroenterology 23 37507075
2024 Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials. BMC cancer 22 38383390
2025 IDO1 inhibition enhances CLDN18.2-CAR-T cell therapy in gastrointestinal cancers by overcoming kynurenine-mediated metabolic suppression in the tumor microenvironment. Journal of translational medicine 19 40045363
2020 The IL1β-HER2-CLDN18/CLDN4 axis mediates lung barrier damage in ARDS. Aging 18 32065780
2024 Enhancing antitumor efficacy of CLDN18.2-directed antibody-drug conjugates through autophagy inhibition in gastric cancer. Cell death discovery 16 39227365
2021 A CLDN18.2-Targeting Bispecific T Cell Co-Stimulatory Activator for Cancer Immunotherapy. Cancer management and research 16 34522140
2023 Development of a Novel CLDN18.2-directed Monoclonal Antibody and Antibody-Drug Conjugate for Treatment of CLDN18.2-Positive Cancers. Molecular cancer therapeutics 15 37788341
2025 The antibody-drug conjugate SHR-A1904 for targeting CLDN18.2 in advanced gastric or gastroesophageal junction cancer: a phase 1 trial. Nature medicine 14 40670772
2024 CD64+ fibroblast-targeted vilanterol and a STING agonist augment CLDN18.2 BiTEs efficacy against pancreatic cancer by reducing desmoplasia and enriching stem-like CD8+ T cells. Gut 14 39187291
2020 Immunophenotype analysis using CLDN18, CDH17, and PAX8 for the subcategorization of endocervical adenocarcinomas in situ: gastric-type, intestinal-type, gastrointestinal-type, and Müllerian-type. Virchows Archiv : an international journal of pathology 14 31932920
2025 A First-in-Human Study of Givastomig, a CLDN18.2 and 4-1BB Bispecific Antibody, as Monotherapy in Patients with CLDN18.2-Positive Advanced or Metastatic Solid Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 13 40586719
2024 Synthesis, preclinical evaluation and pilot clinical translation of [68Ga]Ga-PMD22, a novel nanobody PET probe targeting CLDN18.2 of gastrointestinal cancer. European journal of nuclear medicine and molecular imaging 13 38926162
2018 RHOA mutations and CLDN18-ARHGAP fusions in intestinal-type adenocarcinoma with anastomosing glands of the stomach. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 13 30425335
2023 Screening, Construction, and Preliminary Evaluation of CLDN18.2-Specific Peptides for Noninvasive Molecular Imaging. ACS pharmacology & translational science 12 38093841
2022 Preclinical characterization of a Fab-like CD3/CLDN18.2 XFab® bispecific antibody against solid tumors. Immunobiology 12 36198215
2024 Exploration of radionuclide labeling of a novel scFv-Fc fusion protein targeting CLDN18.2 for tumor diagnosis and treatment. European journal of medicinal chemistry 10 38266552
2024 Immunotherapies targeting the oncogenic fusion gene CLDN18-ARHGAP in gastric cancer. EMBO molecular medicine 10 39164472
2024 Pan-cancer analysis of CLDN18.2 shed new insights on the targeted therapy of upper gastrointestinal tract cancers. Frontiers in pharmacology 10 39555091
2023 Jianpi Yangzheng decoction suppresses gastric cancer progression via modulating the miR-448/CLDN18.2 mediated YAP/TAZ signaling. Journal of ethnopharmacology 10 37023839
2022 ZL-1211 Exhibits Robust Antitumor Activity by Enhancing ADCC and Activating NK Cell-mediated Inflammation in CLDN18.2-High and -Low Expressing Gastric Cancer Models. Cancer research communications 10 36922936
2025 CLDN18.2 CAR-derived Extracellular Vesicle Immunotherapy Improves Outcome in Murine Pancreatic Cancer. Advanced healthcare materials 8 40384272
2025 Landscape Analysis of CLDN18 Expression and Isoform Distribution in Solid Tumors: Insights From MONSTAR-SCREEN-2 Study. Cancer science 8 40455642
2024 Genetically Engineered CLDN18.2 CAR-T Cells Expressing Synthetic PD1/CD28 Fusion Receptors Produced Using a Lentiviral Vector. Journal of microbiology (Seoul, Korea) 8 38700775
2024 The impact of CLDN18.2 expression on effector cells mediating antibody-dependent cellular cytotoxicity in gastric cancer. Scientific reports 8 39095563
2025 A CLDN18.2-Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 40019387
2025 Characterization of early-onset gastritis during zolbetuximab-containing chemotherapy in CLDN18.2-positive gastric cancer. ESMO open 7 41033281
2025 Temporal dynamics of CLDN18.2 expression following zolbetuximab treatment in advanced gastric cancer. ESMO gastrointestinal oncology 7 41647968
2024 A bispecific antibody targeting HER2 and CLDN18.2 eliminates gastric cancer cells expressing dual antigens by enhancing the immune effector function. Investigational new drugs 7 38198061
2023 Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18. American journal of cancer research 7 37693144
2022 Membranous and nuclear staining of CLDN18 in HPV-independent and HPV-associated endocervical adenocarcinomas. Cancer medicine 7 35861118
2024 Preparation of Radiolabeled Zolbetuximab Targeting CLDN18.2 and Its Preliminary Evaluation for Potential Clinical Applications. Molecular pharmaceutics 6 38949095
2025 Noninvasive in vivo tracking of SPIONs-labeled CLDN18.2-targeted CAR-T cells in gastric cancer via magnetic particle imaging. Translational research : the journal of laboratory and clinical medicine 5 40816374
2024 The cost-effectiveness of zolbetuximab in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. Pharmacogenomics 5 38884946
2025 Correlation of CLDN18.2 and Tumor Microenvironment in Gastric Cancer: A Systematic Review. Cancers 3 40647419
2025 Analytical and Clinical Performance of the VENTANA CLDN18 (43-14A) RxDx Assay in Gastric and Gastroesophageal Junction Adenocarcinoma Tissue Samples in SPOTLIGHT and GLOW. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 3 40680855
2025 Targeted Radionuclide Therapy of CLDN18.2-Positive Gastric Cancer with [131I]I-Zolbetuximab: An In Vitro and In Vivo Study. Molecular pharmaceutics 2 40200396
2025 CLDN18.2-targeting STAR-T cell therapy for pancreatic cancer: a strategy to minimize gastric off-tumor toxicity compared to CLDN18.2 CAR-T. Oncogene 2 40301544
2025 CLDN18.2-Targeted Therapy in Gastrointestinal Cancers. Cancers 2 41374966
2024 The small protein LINC01547-ORF inhibits colorectal cancer progression by regulating the CLDN18-FAK-AKT axis. American journal of cancer research 2 39659940
2026 Zolbetuximab as a gastric lineage-directed immunotherapy: mechanistic rationale and translational evidence in CLDN18.2-positive gastroesophageal adenocarcinoma. Expert review of anticancer therapy 1 41521591
2026 Clinicopathological and molecular mechanisms of CLDN18.2 in gastric cancer aggressiveness: a high-risk population study with multi-omics profiling. Journal of pathology and translational medicine 1 41531322
2026 First-line zolbetuximab plus mFOLFOX6 and nivolumab in unresectable CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial. Nature medicine 1 41840238
2025 CLDN18: Clinical, Pathological, and Genetic Signatures with Drug Screening in Gastric Adenocarcinoma. Current medicinal chemistry 1 38639279
2025 Dysregulation of SUSD2-CLDN18.2-mediated cell adhesion contributes to lung adenocarcinoma progression associated with chronic low-dose nanoplastics exposure. Ecotoxicology and environmental safety 1 40882394
2025 Rewiring Antitumor Immunity: Targeting CLDN18.2 with Conditional 4-1BB Activation. Clinical cancer research : an official journal of the American Association for Cancer Research 1 41020763
2025 Zolbetuximab or Immunotherapy as the Initial Targeted Therapy in CLDN18.2-Positive, HER2-Negative Advanced Gastric Cancer: Weighing the Options. Current oncology (Toronto, Ont.) 1 41294710
2026 Preclinical Development and a Case Report of a Nanobody-Based CLDN18.2 CAR-T IMC002 with Reduced On-Target Off-Tumor Toxicity. Molecular cancer therapeutics 0 41208285
2026 KRAS mutation-driven O-GlcNAcylation of CLDN18.2 enhances the progression of pancreatic cancer and reduces the efficacy of CLDN18.2-targeted therapy. Gut 0 41513443
2026 CLDN18.2 in Gastric Cancer: Current Therapeutic Landscape and Future Perspectives. Journal of gastric cancer 0 41517852
2026 Intratumoral heterogeneity and chemotherapy-induced alteration of CLDN18.2 expression in resectable gastric cancer. International journal of clinical oncology 0 41604118
2026 Inhibition of miR-1303 suppresses the development of esophageal cancer by targeting CLDN18. The International journal of biological markers 0 41666080
2026 Trogocytosis-orchestrated CLDN18.2-"dressed" CD8+ T cells drive pancreatic cancer progression via glucose metabolic reprogramming-induced cytotoxicity debilitation and systematic immune senescence cascade. Gut 0 41667243
2026 Development of tri-cistronic CLDN18.2 CAR-T cells incorporating PD-1/CD28 switch and cyclophilin A for enhanced solid tumor immunotherapy. Journal of microbiology (Seoul, Korea) 0 41736320
2026 Preclinical Evaluation of AHT-102, a CLDN18.2 × CD3 Bispecific Antibody: Pharmacokinetics, Anti-Tumor Efficacy, Tissue Distribution, and Safety Profile. Drugs in R&D 0 41746497
2026 Efficacy of CLDN18.2-Targeted Radiotheranostics in Patient-Derived Models of Gastric Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 0 41748291
2026 Expression of CLDN18.2 in Invasive Mucinous Adenocarcinomas of the Lung. Cancer diagnosis & prognosis 0 41778245
2026 CLDN18.2 in lung adenocarcinoma as a promising target of chimeric antigen receptor T cells. Cellular signalling 0 41785979
2026 Immunohistochemical Analysis of Potential Therapeutic Targets PRAME, FOLR1, and CLDN18.2 in Salivary Gland Carcinomas. Cancer medicine 0 41968569
2026 Efficacy and safety of anti-CLDN18.2 therapies in advanced or metastatic gastric, gastro-oesophageal junction, and oesophageal carcinomas with CLDN18.2 positivity: a systematic review and meta-analysis. Future oncology (London, England) 0 41989337
2026 Semiquantitative CLDN18 expression and clinical outcomes in patients with CLDN18-positive gastric cancer treated with zolbetuximab plus chemotherapy. ESMO gastrointestinal oncology 0 41994009
2026 SOT102, a novel CLDN18.2-targeting antibody-drug conjugate, exhibits strong therapeutic potential in solid tumors. BMC cancer 0 42168932
2026 CLDN18 identifies high-risk precursor lesions in gallbladder carcinogenesis: A study of the TFF2⁺ pseudopyloric metaplasia to intestinal metaplasia axis. Virchows Archiv : an international journal of pathology 0 42185594
2025 CLDN18.2: a potential nanotherapeutic target for cholangiocarcinoma. Frontiers in pharmacology 0 40206086
2025 Complete remission of recurrent gastric cancer in a young female patient through CLDN18.2-targeted therapy (LM302) and metastatic ovarian tumor resection: a case report of refractory disease overcoming chemotherapy and immunotherapy resistance. Frontiers in oncology 0 40900784
2025 Impact of concomitant medications on efficacy of CLDN18.2-specific CAR-T cell therapy in advanced gastric cancer. British journal of cancer 0 41318814
2025 Novel syngeneic model of anti-mouse CLDN18.2 CAR -T therapy for gastric cancer demonstrates a synergy with TGF-β and PD-L1 inhibitors. Molecular therapy. Oncology 0 41537163

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