NF-κB signaling mediates acquired resistance after PARP inhibition.

ABSTRACT: PARP inhibitors are a class of promising anti-cancer drugs, with proven activity in BRCA mutant cancers. However, as with other targeted agents, treatment with PARP inhibitors generates acquired resistance within these tumors. The mechanism of this acquired resistance is poorly understood. We established cell lines that are resistant to PARP inhibitor by continuous treatment with the drug, and then used RNA sequencing to compare gene expression. Pathway analysis on the RNA sequencing data indicates that NF-κB signaling is preferentially up-regulated in PARP inhibitor-resistant cells, and that knockdown of core components in NF-κB signaling reverses the sensitivity to PARP inhibitor in resistant cells. Of therapeutic relevance, we show that PARP inhibitor-resistant cells are sensitive to an

SUBMITTER: Nakagawa Y 

PROVIDER: S-EPMC4414156 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature