Abstract 5038: Comparison of the dose response of malignant peripheral nerve sheath tumor in vitro growth inhibition of 30 drugs to reported Cmax values

Abstract

Abstract In this study we aim to identify drugs that can be repurposed to inhibit malignant peripheral nerve sheath tumor (MPNST), a rare and deadly sarcoma associated with Neurofibromatosis type 1 (NF1). Inhibition of MPNST cell growth in vitro was tested for 30 drugs that have previously been through human clinical trials such that the maximum concentration of compound in human serum (Cmax) at the maximum tolerated dose has been determined. Drugs were compared to the chemotherapeutic doxorubicin. Six MPNST cell lines from human and mouse were tested and dose response curves were compared to Cmax for each drug. For most compounds tested, inhibition of MPNST viability occurred at drug concentrations higher than Cmax. Doxorubicin was one of the best compounds tested. Several compounds with less specific molecular targets appear promising, however, currently available inhibitors of receptor tyrosine kinase signaling pathways required concentrations above Cmax to inhibit MPNST viability. These data suggest that difficulty in developing therapy for MPNST may be due to the requirement for high concentrations of drugs to inhibit MPNST cells. Citation Format: Karlyne M. Reilly, Robert G. Tuskan, Brigitte C. Widemann. Comparison of the dose response of malignant peripheral nerve sheath tumor in vitro growth inhibition of 30 drugs to reported Cmax values [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5038. doi:10.1158/1538-7445.AM2017-5038