Abstract IA15: Using gene expression analyses to identify MPNST therapeutics

摘要: Malignant peripheral nerve sheath tumors (MPNST) are rare soft tissue sarcomas that a major source of mortality in neurofibromatosis type 1 (NF1) patients. In NF1 patients, these devastating often develop existing benign neurofibroma. We hypothesized some over-expressed genes solid would be driver and/or mark critical pathways and therapeutic targets. one approach to identify MPNST we targeted 130 up-regulated neurofibroma MPNSTs versus normal cells lentiviral short hairpin (sh) RNA screen. A counter-screen RAS mutant excluded common RAS-pathway driven genes. identified 7 specific for survival MPSNT cells, including the transcription factor MEIS1. second approach, known oncogenes were expressed at higher levels than Aurora Kinase A. responded kinase inhibitor alisertib, combination alisertib HSV1716, virus derived from HSV-1 attenuated by deletion RL1, exhibited significantly increased antitumor efficacy compared either monotherapy. Supported NIH-NS-084855 (N.R. Largaespada, D.), NS-28840 (N.R.), NS-086219 Cripe, T.P.). Citation Format: Nancy Ratner. Using gene expression analyses therapeutics [abstract]. In: Proceedings AACR Conference on Advances Sarcomas: From Basic Science Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA15.