Notch signaling in digestive system cancers: Roles and therapeutic prospects

• Published in: Cellular signalling 2024-12, Vol.124, p.111476, Article 111476
• Main Authors: Liu, Yingru, Gu, Xinyu, Xuan, Mengjuan, Lou, Na, Fu, Leiya, Li, Juan, Xue, Chen
• Format: Article
• Language: English
• Subjects: Animals; Digestive system cancers; Digestive System Neoplasms - drug therapy; Digestive System Neoplasms - metabolism; Digestive System Neoplasms - pathology; Humans; Mechanisms; Notch signaling; Receptors, Notch - metabolism; Role; Signal Transduction; Therapeutic significance
• ISSN: 0898-6568; 1873-3913; 1873-3913
• DOI: 10.1016/j.cellsig.2024.111476

Digestive system cancers rank among the most prevalent malignant tumors, maintaining persistently high incidence and mortality rates. Notch signaling activity, often aberrant in esophageal, gastric, hepatic, pancreatic, and colorectal cancers, plays a pivotal role in the initiation, progression, and therapy resistance of these malignancies. As a highly conserved pathway, Notch signaling is integral to cell differentiation, survival, proliferation, stem cell renewal, development, and morphogenesis. Its dysregulation has been increasingly linked to various diseases, particularly digestive system cancers. In these malignancies, altered Notch signaling influences multiple biological processes, including cell proliferation, invasion, cell cycle progression, immune evasion, drug resistance, and stemness maintenance. Understanding the mechanisms of Notch signaling in digestive system cancers is essential for the development of novel targeted therapies. Numerous Notch pathway-targeting drugs are currently in preclinical studies, demonstrating promising efficacy both as monotherapies and in combination with conventional anti-cancer treatments. This review summarizes recent high-quality findings on the involvement of Notch signaling in digestive system cancers, focusing on the expression changes and pathological mechanisms of its dysregulated components. Special emphasis is placed on the potential of translating Notch-targeted approaches into therapeutic strategies, which hold promise for overcoming the limitations of existing treatments and improving the poor prognosis associated with these cancers. •The Notch signaling pathway plays a role in digestive system cancers through multiple mechanisms.•The review provides a comprehensive overview of Notch signaling in digestive system cancers.•Preclinical studies suggest that Notch inhibitors show promising potential but face challenges such as toxicity, drug resistance, and specificity.•Future research aims to develop more selective Notch-targeted therapies for improved outcomes in digestive system cancers.