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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*  

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 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 CSCs-specific 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.

Affiliation:

Department of Molecular Medicine, Sapienza University of Rome, viale Regina Elena 291, 00161 Rome, Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, viale Regina Elena 291, 00161 Rome, Dipartimento di Scienze ginecologico-ostetriche e Scienze urologiche, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Department of Molecular Medicine, Sapienza University of Rome, viale Regina Elena 291, 00161 Rome, Department of Molecular Medicine, Sapienza University of Rome, viale Regina Elena 291, 00161 Rome, Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, viale Regina Elena 291, 00161 Rome, Department of Biotechnology, Chemistry and Pharmacy, “Department of Excellence 2018-2022”, University of Siena, via Aldo Moro 2, 53100 Siena



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