Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics

Cynthia X. Ma, James W. Janetka, Helen Piwnica-Worms

Research output: Contribution to journalReview article

199 Scopus citations

Abstract

Defects in p53 function, which occur frequently in human cancers due to mutations in TP53 or disruptions in the p53 regulatory pathway, render cells dependent on CHK1 (Checkpoint Kinase 1) to activate cell cycle checkpoints. In the presence of DNA damage or replication stress, inhibition of CHK1 leads to " mitotic catastrophe" and cell death in p53-deficient tumors while sparing p53-proficient cells. CHK1 inhibitors sensitize tumors to a variety of DNA-damaging agents or antimetabolites in preclinical models and are being evaluated in early phase clinical trials. In this review, we summarize recent advances and controversies in the development and application of CHK1 inhibitors as cancer therapeutics.

Original languageEnglish
Pages (from-to)88-96
Number of pages9
JournalTrends in Molecular Medicine
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2011

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