{"entity":{"id":"cldn18-2","kind":"target","name":"Claudin-18.2","aka":["CLDN18.2","claudin 18 isoform 2","CLDN18"],"tldr":"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.","summary":"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.\n\nPositivity 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.\n\nThe 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.","asOf":"2026-09-23","links":[{"label":"CLDN18.2 positivity across pooled SPOTLIGHT and GLOW screening","url":"https://link.springer.com/article/10.1007/s10120-024-01518-1"},{"label":"Single-biopsy sensitivity against whole-section truth, Scientific Reports 2025","url":"https://www.nature.com/articles/s41598-025-12337-4"},{"label":"Multi-laboratory ring trial of CLDN18.2 immunohistochemistry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12647276/"},{"label":"First-in-human CLDN18.2 PET imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11149600/"},{"label":"Gastric cancer biomarker testing review, naming the approved companion assay","url":"https://www.cancerbiomed.org/content/22/3/212"}],"tags":["adc-target","car-t-target","companion diagnostic","gastric"],"related":["opp-cldn18-2-imaging-gastric","her2","ga-68","i-124"],"indications":["gastric-oesophageal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CLDN18","hgnc":"HGNC:2039","ensembl":"ENSG00000066405","uniprot":"P56856","entrez":"51208","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.","whereFound":["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"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"gastric-oesophageal-cancer","pct":"38.4","measure":"moderate-to-strong membranous staining in at least 75% of tumour cells, pooled SPOTLIGHT and GLOW screening","source":"https://link.springer.com/article/10.1007/s10120-024-01518-1"}]},"route":"/targets/cldn18-2/","neighbours":{"opportunity":[{"id":"opp-cldn18-2-imaging-gastric","kind":"opportunity","name":"Claudin-18.2 imaging when one biopsy says negative","route":"/opportunities/opp-cldn18-2-imaging-gastric/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"isotope":[{"id":"ga-68","kind":"isotope","name":"Gallium-68","route":"/isotopes/ga-68/"},{"id":"i-124","kind":"isotope","name":"Iodine-124","route":"/isotopes/i-124/"}],"indication":[{"id":"gastric-oesophageal-cancer","kind":"indication","name":"Gastric and gastro-oesophageal junction adenocarcinoma","route":"/indications/gastric-oesophageal-cancer/"}]}}