Targeting DNA checkpoint kinases in cancer therapy.

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.