Gastric cancer (GC) is highly metastatic and characterized by HER2 amplification. Aberrant HER2 expression drives metastasis, therapy resistance, and tumor recurrence. HER2 amplification contributes to drug resistance by upregulating DNA repair enzymes and drug afflux proteins, reducing drug efficacy. HER2 modulates transcription factors critical for cancer stem cell properties, further impacting drug resistance. HER2 activity is influenced by HER-family ligands, promoting oncogenic signaling. These features point to HER2 as a targetable driver in GC. This review outlines recent advances in HER2-mediated mechanisms and their upstream and downstream signaling pathways in GC. Additionally, it discusses preclinical research investigation that comprehends trastuzumab-sensitizing phytochemicals, chemotherapeutics, and nanoparticles as adjunct therapies. These developments hold promise for improving outcomes and enhancing the management of HER2-positive GC.
Keywords: Adjunct therapies; Gastric cancer; Metastasis; Resistance; Signaling.
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