CLDN18 (Claudin 18)

Growing evidence identifies Claudin18.2 as both a biomarker of aggressive disease and an attractive therapeutic target. Monoclonal antibodies and antibody-drug conjugate directed against Claudin18.2 are currently being evaluated in clinical trials, showing encouraging antitumor activity.

The study indicates that the use of antibiotics for infection reduces the efficacy outcomes of CLDN18.2-specific CAR-T cell therapy for advanced GC, while other concomitant medications do not affect the outcomes. Further research is needed to clarify the optimal administration of these medications and the underlying mechanisms of the gut microbiome in impacting CAR-T treatment response.

CLDN18.2 was not significantly associated with PD-L1 or HER2 status regardless of histological subtype (P > 0.05). This study characterized the histological profile of CLDN18.2-positive G/GEJ and broadened our understanding of subgroups likely to benefit from CLDN18.2-targeted therapy.

GAC may demonstrate distinctive morphology-dependent Claudin 18.2 expression, suggesting potential implications for targeted therapy selection and molecular subtyping. The morphological heterogeneity and aggressive clinical behavior underscore the importance of accurate diagnosis through comprehensive integrated assessment.

Zolbetuximab is associated with high rates of nausea and vomiting during the initial infusion, whereas ICIs are associated with risk of later-onset immune-related toxicities that can be fatal in rare cases. In considering the available evidence, our opinion is that zolbetuximab is a reasonable option for initial targeted treatment in HER2-/CLDN18.2-positive advanced G/GEJ when PD-L1 CPS score is <10 based on the reliability of biomarker testing, comparable OS, and avoidance of potentially irreversible ICI-induced immune toxicity.

Clinicians should monitor albumin levels during treatment and consider nutritional support when indicated. These findings provide important insights for optimizing patient management and ensuring safe conversion surgery planning.

These findings are hypothesis generating and provide rationale for future clinical trials of ADCs and immune checkpoint inhibitors in VSCC. Results suggest HPV-independent tumors may be immunogenically active.

Serial PET imaging with 89Zr-labeled zolbetuximab, an anti-CLDN18.2 monoclonal antibody ([89Zr]Zr-DFO-zolbetuximab), and human IgG ([89Zr]Zr-DFO-IgG) as control (5.5-7.4 MBq) was performed 1, 3, and 6 d after injection, followed by ex vivo analysis of biodistribution... CLDN18.2 could serve as a promising biomarker for precise quantitative imaging and effective treatment of GCa and PDAC. This proof-of-concept study encourages the clinical translation of CLDN18.2 as a radiotheranostic in patients with CLDN18.2-expressing tumors.

IDH1-mutant tumors demonstrated attenuated ADC target expression. These data provide rationale for evaluating ADC strategies in CCA.

On the whole, ADCs offer hope for the treatment of PDAC. Future research and development should focus on improving delivery efficiency, alleviating drug resistance, and individualized design.

Treatment was started with zolbetuximab plus 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX), which is typically used for CLDN18.2-positive gastric cancer, resulting in a partial response. This is the first case of zolbetuximab-based therapy applied to adenocarcinoma from a Meckel's diverticulum with a gastric phenotype due to a biomarker profile of gastric cancer. This case highlights the importance of identifying both the biomarker profile and tissue of origin of the tumor.