Effective sensitization of temozolomide by ABT-888 is lost with development of temozolomide resistance in glioblastoma xenograft lines.

摘要: Resistance to temozolomide (TMZ) and radiotherapy (RT) is a major problem for patients with GBM but may be overcome using the PARP-inhibitor ABT-888. Using two primary xenografts, efficacy of ABT-888 combined RT and/or TMZ was evaluated. Treatment resulted in significant survival prolongation (GBM12: 55.1%, p=0.005; GBM22: 54.4%, p=0.043). had no effect alone, significantly enhanced GBM12 when concurrent RT/TMZ. With multi-cycle therapy, further extended benefit inherently sensitive GBM22 xenograft lines. However, after vivo selection resistance, derivative GBM12TMZ GBM22TMZ lines were longer sensitized by combination TMZ, similar lack observed other resistant tumor Thus, sensitizing effects limited that not been previously exposed these results suggest newly diagnosed more likely respond TMZ/PARP inhibitor therapy than recurrent disease.