Gastric Cancer — Disease Background

Gastric cancer is the fifth most common malignancy globally, with marked geographic variation — highest incidence in East Asia, Eastern Europe, and South America. Helicobacter pylori infection remains the dominant risk factor. Molecular classification (TCGA: EBV+, MSI, GS, CIN subtypes) has revealed actionable therapeutic vulnerabilities.

Treatment advances include trastuzumab for HER2+ disease, nivolumab-based immunotherapy for PD-L1 CPS ≥5, and the emerging Claudin 18.2-targeted approach (zolbetuximab) for CLDN18.2-positive tumors. FGFR2b amplification and MSI-H status represent additional biomarker-guided therapeutic opportunities.

Research Use Only (RUO)

Fig. 1 Major pathogenic pathways in Gastric Cancer

Key Research Targets

HER2 (ERBB2) — HER2 overexpression/amplification occurs in 12-20% of gastric/GEJ adenocarcinoma. Anti-HER2 antibodies support IHC scoring (modified gastric criteria differ from breast cancer), trastuzumab binding competition studies, and T-DXd ADC research extending HER2-targeted therapy to HER2-low gastric cancer.

Claudin 18.2 (CLDN18.2) — Claudin 18.2 is a tight junction protein expressed in approximately 60% of gastric cancers, normally confined to differentiated gastric mucosa. Anti-Claudin 18.2 antibodies enable IHC expression scoring for zolbetuximab eligibility, CAR-T target validation, and tight junction biology studies in gastrointestinal tumors.

PD-L1 (CD274) — PD-L1 combined positive score (CPS ≥5) selects gastric cancer patients for nivolumab/pembrolizumab immunotherapy. Anti-PD-L1 antibodies support CPS validation research, tumor microenvironment immune profiling, and combination immunotherapy studies in gastric/GEJ adenocarcinoma.

FGFR2b — FGFR2b amplification occurs in 5-10% of gastric cancers and represents a targetable receptor tyrosine kinase alteration. Anti-FGFR2 antibodies and recombinant FGFR2b proteins support amplification screening, ligand-binding studies, and bemarituzumab (anti-FGFR2b) mechanism-of-action research.

References

1. Bang Y-J, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy in HER2-positive gastric cancer. Lancet. 2010;376(9742):687-697. DOI

2. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy for advanced gastric cancer. N Engl J Med. 2021;385(25):2372-2381. DOI

3. Shitara K, Lordick F, Bang Y-J, et al. Zolbetuximab plus mFOLFOX6 in CLDN18.2-positive gastric cancer. Nat Med. 2023;29(8):2133-2141. DOI

4. The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202-209. DOI

5. Wainberg ZA, Enzinger PC, Kang Y-K, et al. Bemarituzumab in FGFR2b-selected gastric cancer. Lancet Oncol. 2023;24(11):1233-1246. DOI