Targeting the ATM kinase as a novel strategy for radiosensitizing glioblastoma multiforme in mice

摘要: Glioblastoma multiforme (GBM) is the most lethal type of brain cancer. At best, mean survival is only 12-15 months so an improvement of current therapy is long overdue. Current treatment includes surgery and chemoradiation. The short survival of GBM patients is due, in part, to the innate radioresistance and vicious invasiveness of GBM. ATM, ataxia telangiectasia (A-T) mutated, would be an excellent target for radiosensitizing GBM because of its critical role in regulating the DNA damage response (DDR) and other cellular processes. As a first step towards this goal, we tested the ability of the novel ATM kinase inhibitor KU-60019 to radiosensitize GBM in mice. Using an orthotopic xenograft model of GBM, nude mice were implanted with human glioma cells expressing reporter genes for monitoring tumor growth and spread. KU-60019 was administered intra-cranially by convection-enhanced delivery or by …