ALT neuroblastoma chemoresistance due to telomere dysfunction–induced ATM activation is reversible with ATM inhibitor AZD0156

著者: Balakrishna Koneru, Ahsan Farooqi, Thinh H. Nguyen, Wan Hsi Chen, Ashly Hindle, Cody Eslinger, Monish Ram Makena, Trevor A. Burrow, Joanne Wilson, Aaron Smith, Venkatesh Pilla Reddy, Elaine Cadogan, Stephen T. Durant, C. Patrick Reynolds - Science Translational Medicine 2021 被引用: 58

< 0.0001). AZD0156 showed modest to no enhancement of temozolomide + irinotecan activity in telomerase-positive neuroblastoma cell lines and xenografts. Ataxia telangiectasia and Rad3 related (ATR) inhibition using AZD6738 did not enhance temozolomide + SN-38 activity in ALT neuroblastoma cells. Thus, ALT neuroblastoma chemotherapy resistance occurs via ATM activation and is reversible with ATM inhibitor AZD0156. Combining AZD0156 with temozolomide + irinotecan warrants clinical testing for neuroblastoma.