Poly-ADP-Ribose Polymerase as a Therapeutic Target in Pediatric Diffuse Intrinsic Pontine Glioma and Pediatric High-Grade Astrocytoma

Poly-ADP-Ribose Polymerase as a Therapeutic Target in Pediatric Diffuse Intrinsic Pontine Glioma and Pediatric High-Grade Astrocytoma

Chornenkyy, Y  (2015) Molecular Cancer Therapeutics  (Link to Abstract)


This is a preclinical study (from HSC) looking at PARP (poly-ADP-ribose polymerase) expression and inhibition in DIPG and pHGA.  Using cell culture, tissue microarray, immunohistochemistry and Western Blotting, they found that PARP1 protein is expressed in pHGA and DIPG patient samples and cell lines - 85% of pHGAs and 76% of DIPG tissue microarray samples expressed PARP.  Also they found that Niraparib (an oral PARP inhibitor that has been tested in adult cancer phase 3 trials) is more effective at reducing tumor cell growth than veliparib or olaparib using cell viability kits and colony forming assays.  Niraparib was also shown to cause DNA damage and reduce cell proliferation. Pretreatment with this prior to 2 Gy ionizing radiation decreased DNA damage repair and relative cell count.  In mice xenografts, Niraparib inhibited PARP1 activity and extended the survival of mice pre-treated with Niraparib before IR by 60% (40 vs. 25 days). 


*PARP is demonstrated to be a therapeutic target in DIPG and pHGA.  This study is preclinical rationale for Niraparib, an oral PARP inhibitor, to be further investigated as a radiosensitizer prior to radiation in patients with DIPG and pediatric high-grade astrocytoma.