Immunohistochemical detection of poly(ADP-ribose)polymerase inhibition by ABT-888 in patients withrefractory solid tumors and lymphomas

摘要

Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes involved in multiple cellular processes such as DNA repair, transcriptional regulation, protein degradation, spindle maintenance and apoptosis.1 PARPs, primarily PARP-1 (116-kDa), bind to the sites of single- and double-strand DNA breaks and contribute to the DNA repair through base excision repair and non-homologous end joining.2'3 Upon binding, activated PARP-1 cleaves NAD* into nicotinamide and ADP-ribose that is polymerized onto nuclear proteins including PARP-1 itself (auto-ADP-ribosylation) as well as DNA-binding proteins and histones.4 Poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosyl protein lyase are involved in the catabolism of poly (ADP-ribose), with PARG cleaving ribose-ribose bonds of both linear and branched portions of PAR and the lyase removing proximal ADP-ribose monomers