niraparib and Neuroblastoma

To assess poly (ADP-ribose) polymerase (PARP) inhibitor MK-4827 together with radiation for the treatment of neuroblastoma.. Clonogenic survival assays were used to assess MK-4827, radiation and combination thereof in four neuroblastoma cell lines. In vivo efficacy was tested in a murine xenograft model of metastatic neuroblastoma. In vivo targeted inhibition and biological effects included measurement of cleaved caspase-3, γ-H2AX, and Ki 67 by immunohistochemistry (IHC) and poly-ADP-ribose by Enzyme-Linked Immunosorbent Assay.. Treatment of neuroblastoma cell lines reduced clonogenicity and resulted in additive effects with radiation. In vivo treatment with MK-4827 and radiation prolonged survival (p<0.01) compared to single modalities. In vivo superiority of MK-4827 plus radiation was further documented by significant elevations of cleaved caspase-3 and γ-H2AX in tumors from the combination group compared to single modality cohorts.. Combination of MK-4827 and radiation might provide effective therapy for children with high-risk neuroblastoma.

Topics: Animals; Caspase 3; Cell Line, Tumor; Chemoradiotherapy; Enzyme Inhibitors; Female; Histones; Humans; Indazoles; Mice; Neoplasm Metastasis; Neuroblastoma; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Radiation-Sensitizing Agents