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Updated: Nov 9, 2025
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Notch signaling in cancer: Complexity and challenges on the path to clinical translation
Antonio Ferreira1, Jon C Aster1
1Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, United States.
Abstract:
Notch receptors participate in a conserved pathway in which ligands expressed on neighboring cells trigger a series of proteolytic cleavages that allow the intracellular portion of the receptor to travel to the nucleus and form a short-lived transcription complex that turns on target gene expression. The directness and seeming simplicity of this signaling mechanism belies the complexity of the outcomes of Notch signaling in normal cells, which are highly context and dosage dependent. This complexity is reflected in the diverse roles of Notch in cancers of various types, in which Notch may be oncogenic or tumor suppressive and may have a wide spectrum of effects on tumor cells and stromal elements. This review provides an overview of the roles of Notch in cancer and discusses challenges to clinical translation of Notch targeting agents as well as approaches that may overcome these hurdles.
Insights
Notch signaling, a cell-to-cell communication pathway, plays complex roles in cancer, acting as both oncogenic and tumor suppressive. Understanding its context-dependent effects is key for developing targeted cancer therapies.
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Biology
Background:
- Notch receptors mediate cell-cell communication via ligand-induced proteolytic cleavage.
- The intracellular Notch domain translocates to the nucleus, forming a transcription complex.
- Notch signaling outcomes are highly context and dosage-dependent in normal cellular processes.
Purpose of the Study:
- To review the multifaceted roles of Notch signaling in various cancer types.
- To discuss the challenges in translating Notch-targeting agents into clinical practice.
- To explore potential strategies to overcome these therapeutic hurdles.
Main Methods:
- Literature review of Notch signaling in cancer.
- Analysis of Notch's dual role as oncogene and tumor suppressor.
- Examination of clinical translation challenges and potential solutions.
Main Results:
- Notch signaling exhibits diverse and context-specific effects in cancer.
- It can promote or inhibit tumor development and progression.
- Notch influences both tumor cells and the tumor microenvironment.
Conclusions:
- Notch signaling is a critical, yet complex, player in oncogenesis.
- Clinical application of Notch inhibitors faces significant challenges.
- Further research is needed to optimize Notch-targeted cancer therapies.
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