ATM Mutations in Cancer: Therapeutic Implications

Mol Cancer Ther. 2016 Aug;15(8):1781-91. doi: 10.1158/1535-7163.MCT-15-0945. Epub 2016 Jul 13.


Activation of checkpoint arrest and homologous DNA repair are necessary for maintenance of genomic integrity during DNA replication. Germ-line mutations of the ataxia telangiectasia mutated (ATM) gene result in the well-characterized ataxia telangiectasia syndrome, which manifests with an increased cancer predisposition, including a 20% to 30% lifetime risk of lymphoid, gastric, breast, central nervous system, skin, and other cancers. Somatic ATM mutations or deletions are commonly found in lymphoid malignancies, as well as a variety of solid tumors. Such mutations may result in chemotherapy resistance and adverse prognosis, but may also be exploited by existing or emerging targeted therapies that produce synthetic lethal states. Mol Cancer Ther; 15(8); 1781-91. ©2016 AACR.

Publication types

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

MeSH terms

  • Animals
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia Mutated Proteins / antagonists & inhibitors
  • Ataxia Telangiectasia Mutated Proteins / chemistry
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Drug Resistance, Neoplasm / genetics
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Molecular Targeted Therapy
  • Mutation*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Radiation Tolerance / genetics


  • Protein Kinase Inhibitors
  • Ataxia Telangiectasia Mutated Proteins