Preclinical evaluation of the PARP inhibitor, olaparib, in combination with cytotoxic chemotherapy in pediatric solid tumors.

ABSTRACT:

Background

Poly(ADP-ribose) polymerase (PARP) signals DNA damage and facilitates DNA repair. PARP inhibitors are being evaluated in cancers with defective DNA repair mechanisms or in combination with cytotoxic therapy or radiation. We evaluated the PARP inhibitor, olaparib, in combination with chemotherapy using in vitro and in vivo pediatric solid tumor models.

Procedure

The IC50 of olaparib alone and in combination with cytotoxic agents was determined in 10 pediatric solid tumor cell lines. Synergy was assessed using the combination index of Chou-Talalay. Olaparib alone and in combination with topotecan/cyclophosphamide was evaluated in xenograft models of Ewing sarcoma (RD-ES) and neuroblastoma (NGP). PAR activity was evaluated in cell lines and tumor lysates.

Results<

SUBMITTER: Norris RE 

PROVIDER: S-EPMC3849815 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature