Title:The Development of Ataxia Telangiectasia Mutated Kinase Inhibitors
Volume: 14
Issue: 10
Author(s): Martin Andrs, Jan Korabecny, Eugenie Nepovimova, Daniel Jun, Zdenek Hodny, Simona Moravcova, Hana Hanzlikova and Kamil Kuca
Affiliation:
Keywords:
Ataxia telangiectasia mutated, cancer, chemosensitization, DNA damage response, phosphatidylinositol 3-kinaserelated
protein kinases, radiosensitization.
Abstract: Radiation and genotoxic drugs are two of the cornerstones of current cancer treatment strategy. However, this
type of therapy often suffers from radio- or chemo-resistance caused by DNA repair mechanisms. With the aim of
increasing the efficacy of these treatments, there has been great interest in studying DNA damage responses (DDR).
Among the plethora of signal and effector proteins involved in DDR, three related kinases ATM (ataxia telangiectasia
mutated), ATR (ATM and Rad3-related) and DNA-PK (DNA-dependent protein kinase) play the main roles in initiation
and regulation of signaling pathways in response to DNA double and single strand breaks (DSB and SSB). ATM
inhibitors, as well as those of ATR and DNA-PK, provide an opportunity to sensitize cancer cells to therapy. Moreover,
they can lead to selective killing of cancer cells, exploiting a concept known as synthetic lethality. However, only a very
few selective inhibitors have been identified to this date. This mini-review is focused both on the development of selective
inhibitors of ATM and other inhibitors which have ATM as one of their targets.
