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HER2 阳性与 HER2 阴性乳腺癌的综合进展:揭示分子机制并探索前沿靶向治疗以改善患者预后

英文原题:Comprehensive advances in HER2-positive and HER2-negative breast cancer: unveiling molecular mechanisms and exploring cutting-edge targeted therapies for enhanced patient outcomes.

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Comprehensive advances in HER2-positive and HER2-negative breast cancer: unveiling molecular mechanisms and exploring cutting-edge targeted therapies for enhanced patient outcomes.

PubMed 2025/05/29(内容时间) Naunyn Schmiedebergs Arch Pharmacol Q2 · IF 4(JCR 2025)

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研究概要

HER2 在大约 15-20% 的乳腺癌中过表达或扩增。

中文摘要

人表皮生长因子受体(HER2)属于酪氨酸激酶家族,是乳腺癌患者,尤其是HER2过表达患者的关键治疗靶点。HER2在约15-20%的乳腺癌中过表达或扩增。该家族包括HER1、HER2、HER3和HER4,它们促进癌细胞的生长。参与HER2驱动乳腺癌进展的关键信号通路包括MAPK和mTOR通路,这些通路激活一系列促进DNA合成和细胞生长的因子。HER2癌症发展中的一个关键过程是HER2二聚化,其形成功能性致癌单元,随后关键的是HER2:HER3异二聚化,导致下游信号通路的激活。实体瘤中HER2的改变和ERBB2基因突变推动了精准靶向方法的进展和应用,同时也用于应对传统靶向方法所面临的问题。在本综述中,我们深入讨论了不同的HER2靶向治疗,包括单克隆抗体、抗体药物偶联物、酪氨酸激酶抑制剂、聚(ADP-核糖)聚合酶抑制剂、CDK4/6抑制剂、PET/CT成像靶向的分子探针、癌症疫苗以及细胞疗法如CART-T和CAR-M细胞疗法。其中一些靶向治疗在管理HER2阳性乳腺癌和促进肿瘤消退方面已显示出有效性,而另一些仍在研究中以探索其潜在获益。

展开英文摘要原文

The human epidermal growth factor receptor (HER2), part of the tyrosine kinase family, serves as a key therapeutic target for patients with breast cancer, particularly those with HER2 overexpression. HER2 is overexpressed or amplified in approximately 15-20% of breast cancers. It includes HER1, HER2, HER3, and HER4, which progress the growth of cancerous cells. Key signaling pathways involved in HER2-driven breast cancer progression include the MAPK and mTOR pathways, which activate a cascade of factors that promote DNA synthesis and cell growth. A crucial process in HER2 cancer development is HER2 dimerization, which forms a functional oncogenic unit and is followed crucially by HER2:HER3 heterodimerization that leads to downstream signaling pathways. Alterations in the HER2 in solid tumors and ERBB2 gene mutations have led to advancements and implantation of precision-targeted approaches, as well as to combat the issues from the traditional approaches of targeting. In this review, we have thoroughly discussed different HER2-targeting therapies, which include monoclonal antibodies, antibody-drug conjugates, tyrosine kinase inhibitors, poly (ADP-ribose) polymerase inhibitors, CDK4/6 inhibitors, molecular probes targeting by PET/CT imaging, cancer vaccines, and cell therapies like CART-T and CAR-M cell therapy. Some of these targeted therapies have shown effectiveness in managing HER2-positive breast cancer and promoting tumor regression, while some remain under investigation for their potential benefits.

论文信息

作者
Sood N、Maurya R、Gautam S、Patel P、Das Gupta G、Das Kurmi B
第一作者单位
Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga, 142001, Punjab, India.India
通讯作者单位
Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga, 142001, Punjab, India. bdkurmi@gmail.com.India
文献类型
综述
期刊
Naunyn-Schmiedeberg's archives of pharmacology2025 Nov
原文标识
PubMed 40439885 · DOI 10.1007/s00210-025-04204-w