Cancer Genetics and Epigenetics, 2025, Vol.13, No.1, 41-49 http://medscipublisher.com/index.php/cge 41 Review and Progress Open Access The Role of CRISPR/Cas9 in Targeting HER2-Positive Breast Cancer: Current Research and Future Perspectives Qiyan Lou, Xiaoying Xu Biotechnology Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: xiaoying.xu@cuixi.org Cancer Genetics and Epigenetics, 2025, Vol.13, No.1 doi: 10.5376/cge.2025.13.0005 Received: 27 Dec., 2024 Accepted: 08 Feb., 2025 Published: 23 Feb., 2025 Copyright © 2025 Lou and Xu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Lou Q.Y., and Xu X.Y., 2025, The role of CRISPR/Cas9 in targeting HER2-positive breast cancer: current research and future perspectives, Cancer Genetics and Epigenetics, 13(1): 41-49 (doi: 10.5376/cge.2025.13.0005) Abstract This study explores the therapeutic efficacy and clinical transformation value of CRISPR gene editing technology in HER2 overexpressing breast cancer. This subtype of breast cancer is characterized by high invasiveness and easy recurrence. Although the existing therapies have certain effects, challenges such as treatment resistance still need to be addressed. As a precise genomic regulation tool, CRISPR/Cas9 can specifically intervene in the HER2 gene and its associated core signaling networks (such as the PI3K/AKT and PTEN pathways), effectively inhibiting tumor proliferation and enhancing the therapeutic response. Research data show that the combined application of CRISPR technology with conventional regimens such as chemotherapy and immunotherapy can produce a synergistic gain effect. Despite facing practical obstacles such as off-target risks, stability issues of delivery systems, and ethical controversies, by integrating intelligent algorithms with multi-omics integrated analysis, this technology is accelerating the development of individualized and precise treatment strategies, injecting new impetus into the innovation of the diagnosis and treatment system for HER2-positive breast cancer. Keywords CRISPR/Cas9 gene editing; HER2-overexpressing breast cancer; PI3K/AKT signaling pathway; Treatment resistance; Personalized precision therapy 1 Introduction Breast cancer is a kind of malignant disease with diverse manifestations, and its different subtypes show their own unique biological mechanisms and clinical characteristics. Her2-driven tumors belong to a key clinical subgroup, accounting for approximately 15% to 20% of all breast cancer cases. Abnormal expression of HER2 (human epidermal growth factor receptor 2) can significantly promote the abnormal proliferation of cells. Studies have pointed out that compared with other types, patients with HER2-positive breast cancer often have a faster cell proliferation rate, as well as a stronger tendency of recurrence and metastasis, thereby increasing the difficulty of treatment (Singh et al., 2021; Misra et al., 2023). Therefore, the rapid development of tumors also highlights the urgency of developing specific treatment methods. CRISPR gene editing technology, with its precise genetic modification ability, has profoundly transformed the modern gene manipulation paradigm. This technology has been widely applied in the field of tumor biology research, especially playing a key role in analyzing the molecular characteristic spectrum of breast cancer and developing innovative therapies. It can correct genetic variations related to cancer and regulate dysregulated signal networks, and has become an important technical platform connecting basic research and clinical applications (Sabit et al., 2021; Balon et al., 2022; Rabaan et al., 2023). For HER2-abnormal breast cancer, CRISPR technology helps researchers systematically analyze core signaling axes such as PI3K/AKT/mTOR and BrCA-related regulatory nodes. These pathways often show functional abnormalities in malignant cells (Singh et al., 2021; Misra et al., 2023). These research results lay a theoretical foundation for the development of more targeted therapeutic strategies. This study will explore the latest application trends of CRISPR in HER2-amplified breast cancer and analyze its potential translational application space. This article will bring together the cutting-edge progress in this field and deeply explore its innovative solutions in addressing HER2-related therapeutic challenges. Meanwhile, the key
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