IKK/NF-kappaB Signaling: Balancing Life and Death--A New Approach to Cancer Therapy

J Clin Invest. 2005 Oct;115(10):2625-32. doi: 10.1172/JCI26322.

Abstract

IkappaB kinase/NF-kappaB (IKK/NF-kappaB) signaling pathways play critical roles in a variety of physiological and pathological processes. One function of NF-kappaB is promotion of cell survival through induction of target genes, whose products inhibit components of the apoptotic machinery in normal and cancerous cells. NF-kappaB can also prevent programmed necrosis by inducing genes encoding antioxidant proteins. Regardless of mechanism, many cancer cells, of either epithelial or hematopoietic origin, use NF-kappaB to achieve resistance to anticancer drugs, radiation, and death cytokines. Hence, inhibition of IKK-driven NF-kappaB activation offers a strategy for treatment of different malignancies and can convert inflammation-induced tumor growth to inflammation-induced tumor regression.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / therapeutic use
  • Cell Death / drug effects
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors*
  • I-kappa B Kinase / metabolism
  • I-kappa B Proteins / metabolism*
  • NF-kappa B / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • I-kappa B Proteins
  • NF-kappa B
  • I-kappa B Kinase