The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models
ST Durant, L Zheng, Y Wang, K Chen, L Zhang… - Science …, 2018 - science.org
Poor survival rates of patients with tumors arising from or disseminating into the brain are
attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier
(BBB) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-
resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA
damage response (DDR) to cytotoxic DNA double-strand breaks induced by ionizing
radiation (IR). ATM genetic ablation or pharmacological inhibition results in tumor cell …
attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier
(BBB) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-
resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA
damage response (DDR) to cytotoxic DNA double-strand breaks induced by ionizing
radiation (IR). ATM genetic ablation or pharmacological inhibition results in tumor cell …
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