Cancer stem cells: In the line of fire

Malcolm R. Alison*, Wey Ran Lin, Susan M.L. Lim, Linda J. Nicholson

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

187 Scopus citations

Abstract

Most tumours appear to contain a sub-population (s) of self-renewing and expanding stem cells known as cancer stem cells (CSCs). The CSC model proposes that CSCs are at the apex of a hierarchically organized cell population, somewhat akin to normal tissue organization. Selection pressures may also facilitate the stochastic clonal expansion of sub-sets of cancer cells that may co-exist with CSCs and their progeny, moreover the trait of stemness may be more fluid than hitherto expected, and cells may switch between the stem and non-stem cell state. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In this review we discuss the basis of such resistance that highlights the roles of ABC transporters, aldehyde dehydrogenase (ALDH) activity, intracellular signalling pathways, the DNA damage response, hypoxia and proliferative quiescence as being significant determinants. In the light of such observations, we outline strategies for the successful eradication of CSCs, including targeting the self-renewal controlling pathways (Wnt, Notch and Hedgehog), ALDH activity and ABC transporters, blocking epithelial mesenchymal transition (EMT), differentiation therapy and niche targeting.

Original languageEnglish
Pages (from-to)589-598
Number of pages10
JournalCancer Treatment Reviews
Volume38
Issue number6
DOIs
StatePublished - 10 2012

Keywords

  • ABC transporters
  • ALDH
  • Akt pathway
  • Differentiation therapy
  • Drug resistance
  • EMT
  • Hedgehog signalling
  • Immunodeficient mice
  • Irradiation
  • MicroRNA
  • Notch signalling
  • STAT3
  • Wnt signalling

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