The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy

Expert Opin Ther Targets. 2010 Jan;14(1):45-55. doi: 10.1517/14728220903431069.

Abstract

Importance of the field: Nuclear factor kappa B (NF-kappaB) is activated by a variety of cancer-promoting agents. The reciprocal activation between NF-kappaB and inflammatory cytokines makes NF-kappaB important for inflammation-associated cancer development. Both the constitutive and anticancer therapeutic-induced NF-kappaB activation blunts the anticancer activities of the therapy. Elucidating the roles of NF-kappaB in cancer facilitates developing approaches for cancer prevention and therapy.

Areas covered in this review: By searching PubMed, we summarize the progress of studies on NF-kappaB in carcinogenesis and cancer cells' drug resistance in recent 10 years.

What the reader will gain: The mechanisms by which NF-kappaB activation pathways are activated; the roles and mechanisms of NF-kappaB in cell survival and proliferation, and in carcinogenesis and cancer cells' response to therapy; recent development of NF-kappaB-modulating means and their application in cancer prevention and therapy.

Take home message: NF-kappaB is involved in cancer development, modulating NF-kappaB activation pathways has important implications in cancer prevention and therapy. Due to the complexity of NF-kappaB roles in different cancers, careful evaluation of NF-kappaB's in each cancer type is crucial in this regard. More cancer cell-specific NF-kappaB inhibiting means are desired for improving anticancer efficacy and reducing systemic toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biotransformation / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / genetics
  • Genetic Therapy
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors
  • NF-kappa B / drug effects*
  • NF-kappa B / genetics
  • NF-kappa B / physiology*
  • Neoplasm Metastasis / physiopathology
  • Neoplasm Metastasis / prevention & control
  • Neoplasms / drug therapy*
  • Neoplasms / prevention & control*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Proteasome Endopeptidase Complex / drug effects
  • Signal Transduction / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • DNA, Neoplasm
  • NF-kappa B
  • I-kappa B Kinase
  • Proteasome Endopeptidase Complex