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

• DOI: 10.1016/j.neo.2015.11.014
• Publication Date: 2016-02-29T00:15:15Z
• Authors: Benjamin Lemasson; Hanxiao Wang; Stefanie Galbán; Yinghua Li; Yuan Zhu; Kevin A. Heist; Christina Tsein; Thomas L. Chenevert; Alnawaz Rehemtulla; Craig J. Galbán; Eric C. Holland; Brian D. Ross
• Keywords: Temozolomide; Concomitant; PARP inhibitor

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 IR-induced DNA damage TMZ-induced alkylation at N7-methylguanine N3-methyldenine. However, optimized protocols administration PARP inhibitors have not been delineated. In this study, inhibitor ABT-888 was evaluated combination with compared to current standard-of-care a genetically engineered mouse GBM model. Results demonstrated that concomitant TMZ/IR/ABT-888 adjuvant TMZ/ABT-888 more effective inducing apoptosis reducing proliferation significant tumor growth delay improved overall survival over TMZ/IR TMZ. Diffusion-weighted MRI, an early translatable response biomarker detected changes tumors reflecting 1 day post treatment. This study provides strong scientific rationale development dosing regimen upfront treatment GBM.