Title: PARPi focus the spotlight on replication fork protection in cancer.
Authors: Schlacher, Katharina
Published In Nat Cell Biol, (2017 Oct 31)
Abstract: PARP inhibitors (PARPi) kill BRCA1/2-mutated cancers, which become resistant when DNA repair functions are restored. Now, MUS81 nuclease inhibition due to EZH2 downregulation is found to restore DNA replication fork protection but not repair, leading to PARPi-resistance in mutant BRCA2 cells and patients. This challenges the DNA repair dominance in synthetic lethality.
PubMed ID: 29087384
MeSH Terms: BRCA1 Protein/genetics; BRCA2 Protein/genetics; DNA Damage/drug effects; DNA Damage/genetics; DNA Repair/drug effects; DNA Repair/genetics; DNA Replication/drug effects*; DNA Replication/genetics; Down-Regulation/drug effects; Down-Regulation/genetics; Enhancer of Zeste Homolog 2 Protein/genetics; Humans; Neoplasms/drug therapy*; Neoplasms/genetics*; Neoplasms/metabolism; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology*; Poly(ADP-ribose) Polymerases/metabolism*