REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1656370
Notch Signaling in Cancer: Metabolic Reprogramming and Therapeutic Implications
Provisionally accepted
- 郑州轻工业大学, 河南省, China
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The evolutionarily conserved Notch signaling pathway is essential for cell-fate determination, organogenesis, and tissue homeostasis. Notch receptors and their ligands are transmembrane proteins with epidermal growth factor–like repeats; ligand–receptor binding triggers canonical Notch signaling. Notch signaling is context dependent in cancer, functioning as either an oncogene or a tumor suppressor. Aberrant Notch activation promotes epithelial–mesenchymal transition, sustains cancer stem–like phenotypes, and drives metabolic reprogramming, thereby facilitating tumor progression and therapeutic resistance. Current clinical efforts target the pathway with γ-secretase inhibitors (GSIs), monoclonal and bispecific antibodies, and synthetic Notch (synNotch) approaches. Clinical translation, however, is constrained by dose-limiting toxicity, a paucity of predictive biomarkers, and compensatory resistance through intersecting pathways. Priorities for future work include the development of highly selective Notch modulators, biomarker-guided combination regimens, and targeted delivery systems to realize the translational potential of Notch-targeted therapies in precision oncology.
Keywords: Notch signaling pathway, Cancer, metabolic reprogramming, Tumormicroenvironment, Metabolism
Received: 30 Jun 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Wang, Lv, Nie, Liu, Hou, Chen, Tao, Luo and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shuangshuang Wang, 郑州轻工业大学, 河南省, China
peifeng Li, 郑州轻工业大学, 河南省, China
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