420PD - Systemic Temsirolimus Administration Reduces Tumor Growth in an Orthotopic Mouse Meningioma Model

Abstract

ABSTRACT Disclosure C. Mawrin: Work was supported in part by Pfizer Inc. and the Deutsche Krebshilfe. D. Pachow: work was supported in part by Pfizer Inc. and the Deutsche Krebshilfe. E. Kirches: work was supported in part by Pfizer Inc. and the Deutsche Krebshilfe Meningiomas represent the most frequent intracranial tumors. While most cases correspond to WHO grade I, about 5% belong to the aggressive atypical subtype, and 1% are anaplastic meningiomas with poor clinical outcome. However, even the treatment of benign subtypes might be challenging in recurrent tumors and if complete resection is impossible. So far, no chemotherapy regime has been proven to be effective; radiotherapy is used to treat aggressive meningiomas. We have previously established that human meningiomas have activated mTORC-1 signalling, and that meningioma cells are responsive to mTORC-1 inhibitors. In the present study, we used an orthotopic mouse meningioma model established in our lab to monitore the effect of systemic temsirolimus treatment on meningioma cells grown in the subarachnoidal space. Following orthotopic injection of malignant IOMM-Lee meningioma cells, mice (n = 8) were treated daily with 20mg/kg temsirolimus intraperitoneally for nine days, beginning at day 3. Control animals (n = 8) were treated with diluent only. Tumor growth was monitored by magnetic resonance imaging (MRI). We observed that at day 9, mice treated with temsirolimus had a significantly (p