Browsing by Author "Moore, Jarrett"

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    ATM loss in non-small cell lung cancer: Therapeutic implications for platinum-based therapies
    (2017) Moore, Jarrett; Bebb, Gwyn; Lees-Miller, Susan; Jirik, Frank; Cobb, Jennifer
    Therapeutic strategies for non-small cell lung cancer (NSCLC), such as platinum-based antineoplastic therapies (platins), generate DNA breaks and stimulate DNA damage response pathways. A key component of the response to DNA damage is the protein ataxia telangiectasia mutated (ATM). Evidence from the Glans-Look Database suggests that patients with low tumour ATM protein expression have improved disease-free survival rates after adjuvant platin therapy. I hypothesize that ATM-deficient tumours will be innately sensitive to platin therapies. NSCLC cell lines were treated with increasing concentrations of platins and assessed for ATM activation. ATM knockdown cell lines were generated using shRNA and investigated for cisplatin sensitivity. ATM-proficient cell lines demonstrated increased levels of phosphorylated-ATM in response to platins. ATM knockdowns had increased sensitivity to IR and a trend toward increased sensitivity to cisplatin. It is evident that platin exposure induced an ATM mediated signaling, however the predictive capabilities for ATM-loss to platin sensitivity is still unclear.