Human epidermal growth factor receptor-2 (HER2) is an essential biomarker in oncology. It is highly expressed in many tumors, especially in breast cancer and gastric cancer, and is associated with the malignant progression of tumors. Trastuzumab is a targeted drug for HER2-positive tumors, which can improve the efficacy of HER2-positive tumors, initiate precise treatment of HER2-positive tumors, and play an essential role in first-line therapy and second-line therapy. However, resistance to Trastuzumab is a limiting factor for its efficacy and a necessary factor for short patient survival and poor prognosis. The resistance mechanism to trastuzumab is complex, and non-coding RNA (ncRNA), a type of RNA that does not encode genes, mediates resistance, and plays important roles in of trastuzumab resistance. In clinical practice, ncRNA can be a biomarker for tumor progression, prognosis, and trastuzumab resistance. This article systematically summarizes the key mechanisms of ncRNA resistance to trastuzumab in HER2-positive tumors and its clinical application potential. Especially in this article, for the first time, ncRNA is integrated to regulate of trastuzumab resistance through epigenetic modification crosstalk, insulin-like growth factor 1 receptor (IGF1R) targets, exosome delivery, and ceRNA network regulation aimed to provide insights and references for basic research, drug development, and biomarker determination of trastuzumab resistance in HER2-positive tumors.
Keywords: Cancer; Drug resistance; Mechanism; Trastuzumab; ncRNA.
© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.