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Updated: Jan 30, 2026
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Natural Products Inspired Modulators of Cancer Stem Cells-specific Signaling Pathways Notch and Hedgehog
Rocco Palermo1, Francesca Ghirga2, Maria Grazia Piccioni3
1Department of Molecular Medicine, Sapienza University of Rome, viale Regina Elena 291, Rome 00161, Italy.
Abstract:
It is nowadays widely accepted that some tumors have a niche of cells endowed with stemness features, which may cause resistance to conventional anticancer therapies and relapse/recurrence of the malignancy. These cells are usually referred to as cancer stem cells (CSCs) and, different from normal cancer cells, are rather quiescent. Targeting CSCs is thus a highly challenging but promising strategy to counteract tumor growth, and to develop innovative anticancer agents. Here, we review the chemical, biological and multidisciplinary efforts that have been spent in targeting CSCsspecific signaling pathways Notch and Hedgehog (Hh) for anticancer drug discovery. In particular, the use of natural products as a valuable source of lead compounds or chemical biology tools is emphasized. Examples of natural products functionalization through semi-synthetic transformations or total syntheses, aimed at improving pharmacokinetics and/or pharmacodynamics properties of natural products in Notch or Hh inhibition, are provided as well.
Insights
Targeting cancer stem cells (CSCs) is crucial for overcoming therapy resistance and preventing tumor recurrence. This review highlights natural products and chemical strategies for inhibiting CSC-specific Notch and Hedgehog pathways.
Area of Science:
- Oncology
- Medicinal Chemistry
- Molecular Biology
Background:
- Tumors contain cancer stem cells (CSCs) with stemness features.
- CSCs contribute to therapy resistance and tumor relapse.
- Targeting CSCs is a promising anticancer strategy.
Purpose of the Study:
- To review efforts in targeting CSC-specific Notch and Hedgehog pathways for anticancer drug discovery.
- To emphasize the role of natural products in this field.
- To discuss chemical modifications of natural products for improved efficacy.
Main Methods:
- Review of chemical, biological, and multidisciplinary research.
- Focus on natural products as lead compounds and chemical biology tools.
- Analysis of semi-synthetic and total synthesis approaches for natural product functionalization.
Main Results:
- Natural products offer valuable scaffolds for targeting Notch and Hedgehog pathways.
- Functionalization of natural products can enhance their pharmacokinetic and pharmacodynamic properties.
- This approach holds potential for developing novel anticancer agents.
Conclusions:
- Targeting CSCs via Notch and Hedgehog pathways is a key strategy in cancer therapy.
- Natural products and their derivatives are important resources for developing CSC-targeting drugs.
- Chemical modifications are essential for optimizing natural product-based anticancer agents.
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