Claudin-18.2
A protein that seals the gaps between stomach lining cells. It stays on many stomach cancers as they spread, and two approved treatments are given only to patients whose biopsy shows it.
Overview
Claudin-18 splice variant 2 is a tight-junction protein of the gastric mucosa whose epitope becomes accessible on tumour cells as normal tissue architecture breaks down, making it an unusually tractable target in a cancer with few. It is the selection biomarker for zolbetuximab, approved in the US, EU, Japan and China for CLDN18.2-positive, HER2-negative gastric and gastro-oesophageal junction adenocarcinoma, and in June 2026 China approved satricabtagene autoleucel, a CLDN18.2 CAR-T, in the same biomarker-defined population.
Positivity depends entirely on where the threshold is set. Across 4,507 patients screened for the SPOTLIGHT and GLOW trials, 38.4% were positive at the label threshold of moderate-to-strong membranous staining in at least 75% of tumour cells, and the sponsor reports approximately 35% positivity in Chinese patients with advanced disease. Selection is performed with the VENTANA CLDN18 (43-14A) RxDx assay.
The assay's failure mode is sampling, and it has been quantified. Against whole-tumour-section ground truth a single representative biopsy gave 58.8% sensitivity, rising to 76.5% with six to eight biopsies, and a minimum of six endoscopic biopsies was needed to keep false negatives acceptably low; 18% of tumours were discordant between the primary and a matched nodal metastasis. A multi-laboratory ring trial found a 12% false-negative rate at 91% overall accuracy. That is the gap three Chinese groups are now trying to close with PET: 68Ga-PMD22, 68Ga-NC-BCH and 124I-18B10(10L) each have a published first-in-human pilot of 11 to 17 patients.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A protein that seals the gaps between stomach lining cells. It stays on many stomach cancers as they spread, and two approved treatments are given only to patients whose biopsy shows it.
- 1 · What it is
A protein that seals the gaps between stomach lining cells. It stays on many stomach cancers as they spread, and two approved treatments are given only to patients whose biopsy shows it.
- 2 · What goes wrong in cancer
A tight-junction protein restricted to gastric mucosa in healthy tissue, whose extracellular loop becomes exposed on malignant cells when epithelial polarity is lost.
- 3 · How drugs use it
No product in this corpus aims at Claudin-18.2 yet. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
External identifiers
Companion diagnostics
- VENTANA CLDN18 (43-14A) RxDx Assay · At least 75% of tumour cells with moderate-to-strong membranous staining (zolbetuximab, gastric and gastro-oesophageal junction adenocarcinoma)
Biology
A tight-junction protein restricted to gastric mucosa in healthy tissue, whose extracellular loop becomes exposed on malignant cells when epithelial polarity is lost. Expression is retained in metastases often enough to make it a systemic therapeutic target.
- Gastric and gastro-oesophageal junction adenocarcinoma: 38.4% positive at the 75%-of-cells threshold across 4,507 screened patients
- Pancreatic adenocarcinoma, at lower frequency
- Normal gastric mucosa, where the epitope is not accessible to antibodies
How often this target appears
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Gastric and gastro-oesophageal junction adenocarcinoma | 38.4% | moderate-to-strong membranous staining in at least 75% of tumour cells, pooled SPOTLIGHT and GLOW screening | link.springer.com |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Latest papers
topQuery for this target: (TITLE:"Claudin-18.2" OR ABSTRACT:"Claudin-18.2" OR TITLE:"CLDN18" OR ABSTRACT:"CLDN18" OR TITLE:"CLDN18.2" OR ABSTRACT:"CLDN18.2" OR TITLE:"claudin 18 isoform 2" OR ABSTRACT:"claudin 18 isoform 2") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Claudin-18.2, not a curated reading list.
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