Toward clinical application of the Keap1-Nrf2 pathway

Trends Pharmacol Sci. 2013 Jun;34(6):340-6. doi: 10.1016/j.tips.2013.04.005. Epub 2013 May 9.

Abstract

The Keap1-Nrf2 pathway plays a crucial role in determining the sensitivity of cells to chemical and/or oxidative insults by regulating the basal and inducible expression of detoxification and antioxidant enzymes, ABC transporters, and other stress response enzymes and/or proteins. Increasing attention has been focused on the roles that the Keap1-Nrf2 pathway plays in the protection of our body against drug toxicity and stress-induced diseases. Simultaneously, Nrf2 has been recognized to promote oncogenesis and resistance to chemotherapeutic drugs. Cancer cells hijack Nrf2 activity to support their malignant growth and thus Nrf2 has emerged as a therapeutic target. Translational studies of the Keap1-Nrf2 system, from mechanistic understanding to clinical applications, are now important to improve human health.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2 / agonists
  • NF-E2-Related Factor 2 / antagonists & inhibitors
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress

Substances

  • Antineoplastic Agents
  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human