Zhao Huan, Hu Huihui, Li Zhifei, Xu Mengen, Miao Peipei, Chen Beibei, Chen Xiaobing
Henan University of Traditional Chinese Medicine& Academy of Traditional Chinese Medicines, Zhengzhou, 450046, China.
The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China.
Med Oncol. 2025 Aug 8;42(9):415. doi: 10.1007/s12032-025-02976-y.
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.
人表皮生长因子受体2（HER2）是肿瘤学中的一种重要生物标志物。它在许多肿瘤中高表达，尤其是在乳腺癌和胃癌中，并且与肿瘤的恶性进展相关。曲妥珠单抗是一种针对HER2阳性肿瘤的靶向药物，它可以提高HER2阳性肿瘤的疗效，开启HER2阳性肿瘤的精准治疗，并在一线治疗和二线治疗中发挥重要作用。然而，对曲妥珠单抗的耐药性是其疗效的限制因素，也是患者生存期短和预后不良的一个必然因素。曲妥珠单抗的耐药机制复杂，非编码RNA（ncRNA），一种不编码基因的RNA类型，介导耐药性，并在曲妥珠单抗耐药中发挥重要作用。在临床实践中，ncRNA可以作为肿瘤进展、预后和曲妥珠单抗耐药的生物标志物。本文系统总结了ncRNA在HER2阳性肿瘤中对曲妥珠单抗耐药的关键机制及其临床应用潜力。特别是在本文中，首次整合了ncRNA通过表观遗传修饰串扰、胰岛素样生长因子1受体（IGF1R）靶点、外泌体递送和ceRNA网络调控来调节曲妥珠单抗耐药性，旨在为HER2阳性肿瘤中曲妥珠单抗耐药的基础研究、药物开发和生物标志物测定提供见解和参考。
