Ataxia telangiectasia mutated protein kinase (ATM)

Ataxia telangiectasia mutated protein kinase (ATM) is a serine/threonine protein kinase that plays a central role in the cellular response to DNA damage, particularly double-strand breaks. It is a master regulator of the DNA damage response (DDR). Upon sensing DNA double-strand breaks, it becomes activated and phosphorylates numerous downstream targets involved in cell cycle checkpoints, DNA repair, apoptosis, mitochondrial homeostasis, and regulation of reactive oxygen species. ATM also modulates cellular metabolism and mitochondrial function. Mutations or loss-of-function variants in ATM cause ataxia-telangiectasia, and ATM mutations or repression have been implicated across various cancers due to compromised genome maintenance mechanisms. Inhibitors targeting ATM are being explored for sensitizing tumors to radiotherapy or chemotherapeutics.

ATM inhibitors sensitize tumors with defective DNA damage response to radiotherapy or chemotherapeutics.