Synergistic activity of PARP inhibition by talazoparib (BMN 673) with temozolomide in pediatric cancer models in the pediatric preclinical testing program.

ABSTRACT:

Purpose

Inhibitors of PARP, an enzyme involved in base excision repair, have demonstrated single-agent activity against tumors deficient in homologous repair processes. Ewing sarcoma cells are also sensitive to PARP inhibitors, although the mechanism is not understood. Here, we evaluated the stereo-selective PARP inhibitor, talazoparib (BMN 673), combined with temozolomide or topotecan.

Experimental design

Talazoparib was tested in vitro in combination with temozolomide (0.3-1,000 μmol/L) or topotecan (0.03-100 nmol/L) and in vivo at a dose of 0.1 mg/kg administered twice daily for 5 days combined with temozolomide (30 mg/kg/daily x 5; combination A) or 0.25 mg/kg administered twice daily for 5 days combined with temozolomide (12 mg/kg/daily x 5; combination B). Pharmacodyna

SUBMITTER: Smith MA 

PROVIDER: S-EPMC4587665 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature