Narrative review reveals limited translational efficacy of targeted nanocarriers in gastric cancer, indicating a need for route-specific and subtype-guided design.
Key Points
To assess whether HER2, CLDN18.2, and EGFR serve as viable gateways for targeted nanocarriers in gastric cancer and examine why extensive preclinical work has failed to yield clinical benefits.
Conducted a structured narrative literature search of PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov covering January 2014 to April 2026.
Identified 1,247 records and categorized 186 gastric cancer-specific publications across evidentiary tiers to analyze methodological quality and omissions.
HER2 targeting is constrained by intratumoral heterogeneity and dynamic loss, CLDN18.2 is hindered by tight-junction sequestration and competition from antibody-drug conjugates, and EGFR targeting remains impeded by normal-tissue toxicity and historical trial failures.
Nanocarrier formulations consistently improved tolerability through the removal of toxic solubilizers rather than true tumor-homing effects, while reliance on subcutaneous xenograft models limited translational validity.
Locally administered intraperitoneal nanocarriers targeting peritoneal recurrence demonstrated the strongest translational promise compared to systemic, multi-stimuli-responsive, or exosome-based delivery systems.