NF-κB signaling in cancer stem cells: a promising therapeutic target?

Cell Oncol (Dordr). 2015 Oct;38(5):327-39. doi: 10.1007/s13402-015-0236-6. Epub 2015 Aug 29.

Abstract

Background: Cancer stem cells (CSCs) are regulated by several signaling pathways that ultimately control their maintenance and expansion. NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) forms a protein complex that controls DNA transcription and, as such, plays an important role in proliferation, inflammation, angiogenesis, invasion and metastasis. The NF-κB signaling pathway, which has been found to be constitutively activated in CSCs from a variety of cancers, participates in the maintenance, expansion, proliferation and survival of CSCs. Targeted disruption of this pathway may profoundly impair the adverse phenotype of CSCs and may provide a therapeutic opportunity to remove the CSC fraction. In particular, it may be attractive to use specific NF-κB inhibitors in chronic therapeutic schemes to reduce disease progression. Exceptional low toxicity profiles of these inhibitors are a prerequisite for use in combined treatment regimens and to avoid resistance.

Conclusion: Although still preliminary, recent evidence shows that such targeted strategies may be useful in adjuvant chemo-preventive settings.

Keywords: Cancer stem cells; NF-κB signaling.

Publication types

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

MeSH terms

  • Disease Progression
  • Humans
  • Models, Biological
  • Molecular Targeted Therapy / methods*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Signal Transduction / drug effects*

Substances

  • NF-kappa B