Synthetic lethality in NSCLC cells: Interrogating the therapeutic potential of ATM deficiency
Date
2014-09-29
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Abstract
Previous work by the Bebb and Lees-Miller labs demonstrated poly(ADP)ribose polymerase
inhibitors (PARPi) induced synthetic lethality in Ataxia telangiectasia mutated (ATM) deficient cells. My work extended these studies to non-small cell lung cancer (NSCLC). In vitro, ATM
deficient NSCLC cell lines were investigated by assessing DNA damage-induced phosphorylated target proteins and ionizing radiation (IR) sensitivity using the clonogenic assay. Two cell lines, H23 and H1395, with reduced ATM expression and impaired ATM dependent signalling were
identified. H23 exhibited the expected increased sensitivity to radiation and PARPi. H1395 on the other hand displayed IR-induced ATM dependent phosphorylation and behaved like its ATM competent counterparts by being resistant to the investigative agents. These results suggest that while ATM deficiency may predict sensitivity to radiation and a novel combination of cisplatin and PARPi additional unidentified factors modulate this phenotype. These observations require validation in further studies.
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Citation
Elegbede, A. (2014). Synthetic lethality in NSCLC cells: Interrogating the therapeutic potential of ATM deficiency (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27960