Targeting DNA checkpoint kinases in cancer therapy

Cancer Biol Ther. Jul-Aug 2003;2(4 Suppl 1):S16-22.

Abstract

The DNA damage response includes not only cell cycle arrest and apoptosis, but also direct activation of DNA repair networks. Four DNA checkpoint kinases ATM, ATR, Chk1 and Chk2 have been identified in the mammalian DNA damage response signal transduction pathway. In this article, we review and discuss current knowledge and thinking about checkpoint kinases, and their potential as cancer drug targets. Particular emphasis is given to various therapeutic hypotheses and their promise for improving current cancer therapies.

Publication types

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

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / metabolism
  • Checkpoint Kinase 1
  • Checkpoint Kinase 2
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins
  • Humans
  • Models, Biological
  • Models, Chemical
  • Models, Molecular
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology*
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Protein Kinases
  • Checkpoint Kinase 2
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK1 protein, human
  • CHEK2 protein, human
  • Checkpoint Kinase 1
  • Protein-Serine-Threonine Kinases