Saadh Mohamed J, Omar Thabit Moath, Ballal Suhas, Mahdi Morug Salih, Chahar Mamata, Verma Rajni, A Al-Hussein Rouaida Kadhim, Adil Mohaned, Jawad Mahmood Jasem, Al-Nuaimi Ali M A
Faculty of Pharmacy, Middle East University, Amman 11831, Jordan.
Department of Medical Laboratory Technics, College of Health and Medical Technology, Alnoor University, Mosul, Iraq.
Gene. 2025 Jul 5;955:149461. doi: 10.1016/j.gene.2025.149461. Epub 2025 Mar 29.
The Notch signaling pathway is a fundamental and highly conserved cell-to-cell communication system vital for embryonic development and tissue maintenance. However, its dysregulation has been associated with the initiation, progression, and chemoresistance of various cancers. In this comprehensive review, we will take an in-depth look at the multiple roles of the Notch family in cancer pathogenesis, immune response, and resistance to chemotherapy. We delve into the complicated mechanisms by which Notch signaling promotes tumor growth and development, including its influence on TME remodeling and immune evasion strategies. We will also be discussing recent studies that shed light on the connection between cancer stemness and chemoresistance mediated through the activation of Notch signaling pathways. Elucidation of the interplay between the Notch pathway and major constituents of the TME, including immune cells and cancer-associated fibroblasts, is necessary for the development of targeted therapies against Notch-driven tumors. We further discuss the potential of targeting Notch signaling alone or in combination with standard chemotherapy and immunotherapy as a potent strategy to overcome chemoresistance and improve patient outcomes. We conclude by discussing the challenges and future prospects of using Notch signaling as a therapeutic target in cancer treatment, focusing on how precision medicine and combination approaches are important.
Notch信号通路是一种基本且高度保守的细胞间通讯系统，对胚胎发育和组织维持至关重要。然而，其失调与各种癌症的发生、发展及化疗耐药性有关。在这篇全面综述中，我们将深入探讨Notch家族在癌症发病机制、免疫反应和化疗耐药性中的多重作用。我们深入研究Notch信号促进肿瘤生长和发展的复杂机制，包括其对肿瘤微环境重塑和免疫逃逸策略的影响。我们还将讨论近期研究，这些研究揭示了通过Notch信号通路激活介导的癌症干性与化疗耐药性之间的联系。阐明Notch通路与肿瘤微环境的主要成分（包括免疫细胞和癌症相关成纤维细胞）之间的相互作用，对于开发针对Notch驱动肿瘤的靶向治疗至关重要。我们进一步讨论单独靶向Notch信号或与标准化疗和免疫疗法联合使用作为克服化疗耐药性和改善患者预后的有效策略的潜力。我们通过讨论将Notch信号作为癌症治疗中的治疗靶点所面临的挑战和未来前景来结束本文，重点关注精准医学和联合方法的重要性。
