The ATM regulated DNA damage response pathway as a chemo- and radiosensitisation target

Abstract

Background: Ataxia telangiectasia mutated (ATM) kinase plays a central role in maintaining genomic stability and regulating the response of cells exposed to agents that induce DNA damage. ATM regulated pathways also enable cancer cells to resist the lethal effects of genotoxic cancer treatments. The pharmacological inhibition of these pathways may thus sensitise cancer cells to chemo- and radiotherapy. Objectives: This review outlines the role of ATM in regulating components of the DNA damage response pathway. The potential of inhibitors that target ATM regulated pathways to act as chemo- and radiosensitising agents is also discussed. Results/conclusions: Inhibitors that target ATM and its downstream targets are likely to be effective as chemo- and/ or radiosensitising agents. Their effective use will, however, require a better understanding of when and how ATM influences the sensitivity of cancer cells to particular genotoxic agents.

Keywords::

• ATM
• cancer therapy
• chemosensitisation
• DNA damage checkpoint
• radiosensitisation