From Antibody Drugs to RNA Interference and Nanotherapy: The Evolution and Integration of Targeted Strategies in Gastric Cancer.

Gastric cancer is a leading cause of cancer death worldwide. Targeted therapy is shifting from blocking signaling pathways to precise gene regulation. This review covers three key areas: antibody drugs, RNAi, and nanocarriers. Anti-HER2 agents, VEGFR2 inhibitors, Claudin 18.2-directed therapies and PD-1/PD-L1 inhibitors improve survival in biomarker-selected patients-but resistance and low response rates (ORR < 20% in unselected groups) limit their use. RNAi silences key oncogenes to reverse chemoresistance and reprogram the immunosuppressive tumor microenvironment, but it suffers from rapid degradation, poor endosomal escape, off-target effects, and weak tumor penetration. Nanocarrier systems-including lipid nanoparticles (LNPs), stimuli-responsive micelles, and mesoporous silica-combined with aptamers enable targeted delivery of therapeutic antibodies and siRNA, penetration across stromal barriers, and controlled, tumor microenvironment-triggered cargo release. Altogether, the future of gastric cancer therapy is moving beyond monotherapy to a five-part strategy: antibody targeting, RNA silencing, nanocarrier delivery, AI-guided decisions, and immune remodeling.