Cancer stem cells and therapeutic perspectives

E. Galmozzi, F. Facchetti, Caterina A M La Porta

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell proprieties. Stem cells are defined as cells which are able to both extensively self-renew and differentiate into progenitors. Furthermore, stem cells are also attractive candidates as origin of cancers, as in their long lifespan mutations and epigenetic changes they can increase allowing for increasing evolution toward malignancy. Herein, we discuss the evidences reported in literature on existence of cancer stem cells in several tumors and mechanisms of the extrinsic and intrinsic circuitry controlling stem cell fate as well as their possible connections to cancer. In particular, the review will focus on recent results on conserved Polycomb Group (PcG) gene family, an epigenetic chromatin modifiers involved in cancer development and also in the maintenance of embryonic and adult stem cells. There are two distinct multiprotein PcG complexes identified, Polycomb repressive complex (PRC) 1 and 2. The fact that either PRC1 Bmi1 than PRC2 SU(Z)12 components are implicated in self-renewal stem cells and up-regulated in several kind of human cancer, confirm the importance of (de)regulation of the PcG genes in cancer and stem cell biology. Moreover, Bmi1 and SU(Z)12 are downstream target of Sonic hedgehog (Shh) and Wnt signaling respectively, providing for a connection between epigenetic change regulators (PcG) and developmental-signaling pathways. Finally, potential therapies using inhibitors acting on cancer stem cell population such as cyclopamine, an inhibitor of hedgehog signalling, 6-bromoindirubin-3′-oxime (BIO) which acts on GSK3 and inhibitors of β-catenin signaling such as exisulind and the tyrosine-kinase inhibitor STI571/Gleevac/imatinib will also discuss.

Original languageEnglish
Pages (from-to)603-607
Number of pages5
JournalCurrent Medicinal Chemistry
Volume13
Issue number6
DOIs
Publication statusPublished - Mar 2006

Fingerprint

Neoplastic Stem Cells
Stem cells
Stem Cells
Epigenomics
Neoplasms
Polycomb Repressive Complex 1
Polycomb Repressive Complex 2
Therapeutics
Catenins
Adult Stem Cells
Embryonic Stem Cells
Protein-Tyrosine Kinases
Genes
Chromatin
Cell Biology
Cytology
Clone Cells
Maintenance
Deregulation
Mutation

Keywords

  • Acute lymphoid leukemia
  • Cyclopamine
  • Drug-resistant variants
  • Hh signaling
  • Medulloblastomas
  • Polycomb-group (PcG)

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Cancer stem cells and therapeutic perspectives. / Galmozzi, E.; Facchetti, F.; La Porta, Caterina A M.

In: Current Medicinal Chemistry, Vol. 13, No. 6, 03.2006, p. 603-607.

Research output: Contribution to journalArticle

Galmozzi, E. ; Facchetti, F. ; La Porta, Caterina A M. / Cancer stem cells and therapeutic perspectives. In: Current Medicinal Chemistry. 2006 ; Vol. 13, No. 6. pp. 603-607.
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