Replication Stress: An Achilles' Heel of Glioma Cancer Stem-like Cells

Glioblastoma (GBM) is a highly aggressive form of cancer that is resistant to standard therapy with concurrent radiation and temozolomide, two agents that work by inducing DNA damage. An underlying cause of this resistance may be a subpopulation of cancer stem-like cells that display a heightened DNA damage response (DDR). Although this DDR represents an attractive therapeutic target for overcoming the resistance of GBMs to radiotherapy, until now, the cause of this DDR upregulation has not been understood. In a previous issue of Cancer Research, Carruthers and colleagues investigated DNA replication stress as an underlying mechanism responsible for upregulation of the DDR and hence the radiation resistance of glioma stem-like cells. Furthermore, the authors explore the efficacy of combined ataxia telangiectasia and Rad3-related kinase and PARP inhibitors as a strategy to leverage these mechanisms and overcome radiation resistance. (C) 2018 AACR.