Ontology highlight
ABSTRACT:
SUBMITTER: Ning JF
PROVIDER: S-EPMC6606647 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Ning Jian-Fang JF Stanciu Monica M Humphrey Melissa R MR Gorham Joshua J Wakimoto Hiroko H Nishihara Reiko R Lees Jacqueline J Zou Lee L Martuza Robert L RL Wakimoto Hiroaki H Rabkin Samuel D SD
Nature communications 20190702 1
PARP inhibitors (PARPis) have clinical efficacy in BRCA-deficient cancers, but not BRCA-intact tumors, including glioblastoma (GBM). We show that MYC or MYCN amplification in patient-derived glioblastoma stem-like cells (GSCs) generates sensitivity to PARPi via Myc-mediated transcriptional repression of CDK18, while most tumors without amplification are not sensitive. In response to PARPi, CDK18 facilitates ATR activation by interacting with ATR and regulating ATR-Rad9/ATR-ETAA1 interactions; th ...[more]