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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Natural Products Inspired Modulators of Cancer Stem Cells-specific Signaling Pathways Notch and Hedgehog

Author(s): Rocco Palermo, Francesca Ghirga, Maria Grazia Piccioni, Flavia Bernardi, Nadezda Zhdanovskaya, Paola Infante* and Mattia Mori*

Volume 24 , Issue 36 , 2018

Page: [4251 - 4269] Pages: 19

DOI: 10.2174/1381612825666190111124822

Price: $65


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.

Keywords: Cancer, cancer stem cells, natural products, drug discovery, Notch, Hedgehog, inhibitors.

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