Enhanced efficacy of combined HDAC and PARP targeting in glioblastoma.

ABSTRACT: Recent clinical trials have demonstrated that targeting chromatin remodeling factors is as a promising strategy for the treatment of glioblastoma (GBM). We and others have shown constitutive activation of DNA damage response (DDR) pathways in gliomas and suggested that targeting the DDR may improve the currently grim prognosis for patients. Based on our previous findings that inhibition of poly(ADP-ribose) polymerase (PARP) increases radio-sensitivity of the notoriously radio-resistant GBM cells, we hypothesized that epigenetic down-regulation of the DDR responses and induction of oxidative stress via HDAC inhibition would contribute to more efficient targeting of this deadly disease. Our data show that SAHA, an HDAC class I + II inhibitor, in combination with olaparib (PARP inhibitor): i)

SUBMITTER: Rasmussen RD 

PROVIDER: S-EPMC5423160 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature