CLDN18 (Claudin 18)

Digital image analysis, radiomics, and machine learning are likely to improve quantification and may support future biomarker integration. A practical pathology-oriented approach should prioritize tissue stewardship, conservative interpretation of IHC results, and close coordination with molecular methods.

Finally, we critically assess translational barriers, including organ-specific metastatic tropism and resistance evolution, and propose that the convergence of deep molecular profiling, neural-immune modulation, and AI-enabled computational oncology will be central to advancing precision medicine for GC. This integrated framework aims to accelerate the development of mechanism-based combination therapies.

P1/2, N=42, Recruiting, Beijing Biotech

The patient was treated with combination chemotherapy and immune checkpoint inhibition. This case highlights an atypical presentation of advanced gastroesophageal junction adenocarcinoma in a young adult and underscores the importance of early endoscopic evaluation in patients with persistent dysphagia, as well as recognition of uncommon metastatic patterns and the therapeutic implications of biomarker profiling.

P2, N=389, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

P1/2, N=36, Recruiting, Beijing Biotech

Background: Claudin 18.2 (CLDN18.2) has become a clinically relevant therapeutic target in gastric adenocarcinoma (GC), with zolbetuximab now approved for use in CLDN18.2-positive, HER2-negative advanced disease... CLDN18.2 shows excellent intratumoral reproducibility and a stable biological profile in GC, supporting its diagnostic reliability in biopsies and value as a predictive biomarker. A subset with extreme expression demonstrated aggressive features, suggesting a potential "claudin-driven" phenotype requiring further study.

To confirm encouraging first clinical data, larger studies specific for BTC are needed to address tumor heterogeneity and to determine cutoff levels of CLDN-18.2 expression. Such studies are also needed to understand combination options and sequencing of therapies and to further validate novel approaches to fully exploit the potential of targeting CLDN-18.2 in BTC.

P2, N=90, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

B7-H3 was identified as the only consistently and strongly expressed surface antigen in a clinically heterogeneous MTC cohort. These findings identify B7-H3 as a potential therapeutic opportunity for advanced MTC and underscore the limited number of targetable surface antigens in this disease.

Immunomodulatory therapy with anakinra was initiated; however, persistent severe thrombocytopenia precluded systemic oncologic therapy. The patient died 28 days after admission from multiorgan failure, highlighting the fulminant course and high mortality associated with malignancy-triggered HLH. This case highlights the importance of early consideration of malignancy in unexplained HLH and illustrates how hematologic compromise may preclude disease-modifying treatment.

Finally, the authors explore future directions, including biomarker-driven patient selection, integration into earlier lines of therapy, and innovative formats designed to widen the therapeutic window. With continued advances in engineering and clinical development, ADCs are poised to expand their role from salvage settings to frontline treatment, offering the potential for deeper and more durable responses across a broad spectrum of solid tumors.