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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Claudin 18.2 is a tight-junction protein normally hidden inside stomach lining cells that becomes exposed on the surface of many stomach cancers. Zolbetuximab, an antibody against it, added to chemotherapy lengthens survival in tumours that express it strongly, and antibody-drug conjugates and CAR-T cells against the same target are in trials.
Claudin 18.2 is a tight-junction protein confined to the gastric mucosa in normal tissue; during malignant transformation the junctions break down and the protein is exposed on the cell surface, where an antibody can reach it. Expression is tested by immunohistochemistry with the 43-14A antibody, and the trial-defined positive threshold is moderate-to-strong membranous staining in at least 75 percent of tumour cells. Expression is retained in metastases and is as common in diffuse-type as in intestinal-type tumours, so it is the one target that reaches the poor-prognosis diffuse subgroup; HER2 and claudin 18.2 positivity rarely overlap.
Zolbetuximab, a chimeric IgG1 antibody that kills claudin 18.2-positive cells through antibody-dependent cytotoxicity and complement, was tested in two phase 3 trials in HER2-negative, claudin 18.2-positive advanced disease. SPOTLIGHT (Lancet 2023) added it to FOLFOX and extended median progression-free survival from 8.7 to 10.6 months and median overall survival from 15.5 to 18.2 months; GLOW (Nature Medicine 2023) added it to CAPOX and extended survival from 12.2 to 14.4 months. Japan approved zolbetuximab in March 2024, the FDA in October 2024 and Europe later that year; nausea and vomiting in the first cycles, from on-target binding to normal stomach lining, are its characteristic toxicity and are managed with slower infusion and antiemetics.
| Setting | Approach | Guideline |
|---|---|---|
| Advanced, first line | Zolbetuximab with FOLFOX (SPOTLIGHT) or CAPOX (GLOW) in HER2-negative, claudin 18.2-positive disease; nivolumab or pembrolizumab with chemotherapy remains an alternative where PD-L1 is high. | not mapped |
| Second line | Ramucirumab with paclitaxel; claudin 18.2 antibody-drug conjugates and CAR-T in trials. | not mapped |
| Toxicity management | Antiemetic prophylaxis and slowed infusion for the nausea and vomiting of the first cycles. | not mapped |