Fu Leiya, Gu Xinyu, Lou Na, Li Juan, Xue Chen
Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China.
Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471000, Henan, China.
Eur J Med Res. 2025 May 20;30(1):402. doi: 10.1186/s40001-025-02626-z.
Notch signaling is a widely preserved communication pathway that supports essential cellular functions by allowing adjacent cells to interact. The Notch signaling pathway consists of Notch ligands (DSL proteins), Notch receptors, DNA-binding proteins, and downstream target genes. Hepatocellular carcinoma (HCC) represents the predominant cause of cancer-related deaths globally and poses a significant threat to human health. For highly malignant HCC, current treatment options, including chemotherapy, radiotherapy, immunotherapy, targeted therapies, and surgical procedures, often have poor prognoses. Therefore, there is a need to explore additional therapeutic strategies. Many studies have found that abnormal activation of the Notch signaling pathway contributes to tumor initiation and progression by promoting HCC proliferation, metastasis, stem cell-like properties, and drug resistance. In this research, we reveal the composition and activation mechanisms of the Notch signaling pathway, as well as the molecular mechanism underlying its aberrant activation in HCC. Furthermore, we summarize recent advances in targeting Notch signaling for the treatment of HCC. This review aims to highlight the promising potential of investigating the Notch pathway as a therapeutic target in HCC.
Notch信号通路是一种广泛保守的信号传导途径,通过允许相邻细胞相互作用来支持重要的细胞功能。Notch信号通路由Notch配体(DSL蛋白)、Notch受体、DNA结合蛋白和下游靶基因组成。肝细胞癌(HCC)是全球癌症相关死亡的主要原因,对人类健康构成重大威胁。对于高恶性HCC,目前的治疗选择,包括化疗、放疗、免疫疗法、靶向治疗和手术,预后往往较差。因此,有必要探索其他治疗策略。许多研究发现,Notch信号通路的异常激活通过促进HCC增殖、转移、干细胞样特性和耐药性,促进肿瘤的发生和发展。在本研究中,我们揭示了Notch信号通路的组成和激活机制,以及其在HCC中异常激活的分子机制。此外,我们总结了靶向Notch信号通路治疗HCC的最新进展。本综述旨在强调将Notch通路作为HCC治疗靶点进行研究的潜在前景。