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<p>Colorectal cancer (CRC) represents a major global health challenge, marked by a high mortality rate and a strong association with aging. A key factor contributing to the progression of this malignancy is the overactivation of oncogenic signaling pathways. Notch signaling is a conversed pathway. This pathway utilizes a distinct mechanism that relies on direct cell-to-cell interactions for activation. Notch signaling ligands and receptors possess unique biological functions and distinct structures. Aberrant Notch signaling plays a pivotal role in CRC progression. It coordinates diverse oncogenic programs, including sustained proliferative signaling, invasive behavior, cancer stem cell maintenance, acquisition of therapeutic resistance, and the promotion of angiogenesis through increased microvascular density. The interplay between Notch signaling and other oncogenic pathways leads to the development of CRC. Designing therapeutic agents that target the Notch pathway is a feasible strategy to mitigate the oncogenic features associated with CRC progression. Furthermore, assessing the components of this pathway can serve as a diagnostic biomarker and offer insights into patient prognosis. Predicting the response to treatment is another clinical application of Notch evaluation. This review delves into the multi-layered roles of Notch signaling in CRC.</p>

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Decoding notch signaling pathway: an updated insight into its role in colorectal cancer progression and therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月30日

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  • Mehran Molavand,
  • Azita Asadi,
  • Maryam Majidinia,
  • Bahman Yousefi

摘要

Colorectal cancer (CRC) represents a major global health challenge, marked by a high mortality rate and a strong association with aging. A key factor contributing to the progression of this malignancy is the overactivation of oncogenic signaling pathways. Notch signaling is a conversed pathway. This pathway utilizes a distinct mechanism that relies on direct cell-to-cell interactions for activation. Notch signaling ligands and receptors possess unique biological functions and distinct structures. Aberrant Notch signaling plays a pivotal role in CRC progression. It coordinates diverse oncogenic programs, including sustained proliferative signaling, invasive behavior, cancer stem cell maintenance, acquisition of therapeutic resistance, and the promotion of angiogenesis through increased microvascular density. The interplay between Notch signaling and other oncogenic pathways leads to the development of CRC. Designing therapeutic agents that target the Notch pathway is a feasible strategy to mitigate the oncogenic features associated with CRC progression. Furthermore, assessing the components of this pathway can serve as a diagnostic biomarker and offer insights into patient prognosis. Predicting the response to treatment is another clinical application of Notch evaluation. This review delves into the multi-layered roles of Notch signaling in CRC.