Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Previously Published Works bannerUCSF

Poly (ADP-Ribose) polymerase inhibitor MK-4827 together with radiation as a novel therapy for metastatic neuroblastoma.

Abstract

Background/aim

To assess poly (ADP-ribose) polymerase (PARP) inhibitor MK-4827 together with radiation for the treatment of neuroblastoma.

Materials and methods

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.

Results

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.

Conclusion

Combination of MK-4827 and radiation might provide effective therapy for children with high-risk neuroblastoma.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View