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

期刊

CURRENT PHARMACEUTICAL DESIGN
卷 24, 期 36, 页码 4251-4269

出版社

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612825666190111124822

关键词

Cancer; cancer stem cells; natural products; drug discovery; Notch; Hedgehog; inhibitors

资金

  1. Italian Ministry of Education, University and Research - Dipartimenti di Eccellenza [L. 232/2016]

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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 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.

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