Trastuzumab Deruxtecan Targets HER2 in the Treatment of Gastric Cancer
TL;DR
Systematic theoretical support for stratified clinical administration and novel ADC structural optimization for HER2-mutated gastric malignant tumors is provided.
Abstract
Gastric cancer presents high global mortality, and traditional chemotherapy and single-target agents are limited by frequent drug resistance and unsatisfactory tumor inhibition efficiency. This paper systematically sorts gastric cancer's Correa cascade carcinogenic process and core oncogenic signaling axes, then elaborates the complete structural composition and multi-layer anti-tumor mechanism of the novel antibody-drug conjugate trastuzumab deruxtecan (T-DXd). T-DXd binds HER2 specifically via monoclonal antibody fragments, releases topoisomerase inhibitor DXd after lysosomal cleavage of cleavable GGFG linkers, and eliminates adjacent HER-low/negative tumor cells through the bystander killing effect. Multiple DESTINY-Gastric Phase II trials confirm T-DXd achieves significantly higher objective response and longer overall survival than standard chemotherapy regimens in HER2-positive advanced gastric cancer, with controllable adverse reactions. Current clinical transformation obstacles mainly include interstitial lung disease risk and diverse acquired resistance subtypes. This paper provides systematic theoretical support for stratified clinical administration and novel ADC structural optimization for HER2-mutated gastric malignant tumors.