HER2-positive gastric cancer is an aggressive malignancy that frequently develops resistance to trastuzumab therapy. A key mechanism underlying this resistance is activation of the PI3K/AKT/mTOR signaling pathway, which enhances tumor cell survival, proliferation, angiogenesis, and ultimately leads to treatment failure and disease progression.
This article comprehensively reviews trastuzumab resistance from molecular mechanisms to clinical evidence. It integrates current knowledge of signaling pathways involved in resistance and highlights emerging therapeutic strategies, including targeted agents and combination therapies. Importantly, the study proposes a structured disease treatment algorithm for HER2-positive gastric cancer, linking molecular mechanisms with clinical decision-making and future precision oncology approaches.
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