Therapy resistance mediated by cancer stem cells

Semin Cancer Biol. 2018 Dec;53:156-167. doi: 10.1016/j.semcancer.2018.11.006. Epub 2018 Nov 22.


Cancer stem cells (CSC) possess abilities generally associated with embryonic or adult stem cells, especially self-renewal and differentiation. The CSC model assumes that this subpopulation of cells sustains malignant growth, which suggests a hierarchical organization of tumors in which CSCs are on top and responsible for the generation of intratumoral heterogeneity. Effective tumor therapy requires the eradication of CSC as they can support regrowth of the tumor resulting in recurrence. However, eradication of CSC is difficult because they frequently are therapy resistant. Therapy resistance is mediated by the acquisition of dormancy, increased DNA repair and drug efflux capacity, decreased apoptosis as well as the interaction between CSC and their supporting microenvironment, the CSC niche. This review highlights the role of CSC in chemo- and radiotherapy resistance as well as possible ways to overcome CSC mediated therapy resistance.

Keywords: Cancer stem cells; DNA repair; Dormancy; EMT; Stem cell niche.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Chemoradiotherapy
  • DNA Repair / genetics
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / radiation effects
  • Radiation Tolerance / drug effects
  • Radiation Tolerance / genetics*
  • Telmisartan / therapeutic use


  • ATP-Binding Cassette Transporters
  • Telmisartan