|作者：||Victoria Dunne, Mihaela Ghita, Donna M. Small, Caroline B.M. Coffey, Sinead Weldon, Clifford C. Taggart, Sarah O. Osman, Conor K. McGarry, Kevin M. Prise, Gerard G. Hanna, Karl T. Butterworth|
1Centre for Cancer Research and Cell Biology, Queen’s University Belfast, UK
2Centre for Experimental Medicine, Queen’s University Belfast, UK
3Northern Ireland Cancer Centre, Queen’s University Belfast, UK
|刊名：||Radiotherapy and Oncology, 2017|
|关键词：||Ataxia telangiectasia related-3 (ATR); AZD6738; DNA damage response; Non-small cell lung cancer (NSCLC); Fibrosis; Small animal radiotherapy research platform (SARRP);|
Abstract(#br)Background and purpose(#br)To evaluate the impact of ATR inhibition using AZD6738 in combination with radiotherapy on the response of non-small cell lung cancer (NSCLC) tumour models and a murine model of radiation induced fibrosis.(#br)Materials and methods(#br)AZD6738 was evaluated as a monotherapy and in combination with radiation in vitro and in vivo using A549 and H460 NSCLC models. Radiation induced pulmonary fibrosis was evaluated by cone beam computed tomography (CBCT) and histological staining.(#br)Results(#br)AZD6738 specifically inhibits ATR kinase and enhanced radiobiological response in NSCLC models but not in human bronchial epithelial cells (HBECs) in vitro . Significant tumour growth delay was observed in cell line derived xenografts (CDXs) of H460 cells ( p...