%0 Journal Article
%T Evaluation of Concurrent Radiation, Temozolomide and ABT-888 Treatment Followed by Maintenance Therapy with Temozolomide and ABT-888 in a Genetically Engineered Glioblastoma Mouse Model
%A Alnawaz Rehemtulla
%A Benjamin Lemasson
%A Brian D. Ross
%A Christina Tsein
%A Craig J. Galb¨˘n
%A Eric C. Holland
%A Hanxiao Wang
%A Kevin A. Heist
%A Stefanie Galb¨˘n
%A Thomas L. Chenevert
%A Yinghua Li
%A Yuan Zhu
%J Archive of "Neoplasia (New York, N.Y.)".
%D 2016
%R 10.1016/j.neo.2015.11.014
%X Despite the use of ionizing radiation (IR) and temozolomide (TMZ), outcome for glioblastoma (GBM) patients remains dismal. Poly (ADP-ribose) polymerase (PARP) is important in repair pathways for IR-induced DNA damage and TMZ-induced alkylation at N7-methylguanine and N3-methyldenine. However, optimized protocols for administration of PARP inhibitors have not been delineated. In this study, the PARP inhibitor ABT-888 was evaluated in combination with and compared to current standard-of-care in a genetically engineered mouse GBM model. Results demonstrated that concomitant TMZ/IR/ABT-888 with adjuvant TMZ/ABT-888 was more effective in inducing apoptosis and reducing proliferation with significant tumor growth delay and improved overall survival over concomitant TMZ/IR with adjuvant TMZ. Diffusion-weighted MRI, an early translatable response biomarker detected changes in tumors reflecting response at 1 day post TMZ/IR/ABT-888 treatment. This study provides strong scientific rationale for the development of an optimized dosing regimen for a PARP inhibitor with TMZ/IR for upfront treatment of GBM
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005260/