Total loss of NF1 in neurofibroma Schwann cells leads to increased quantities of Ras GTP known to activate Raf kinase, phosphatidylinositol 3 kinase, and other signals, regulating cell pan Aurora Kinase inhibitor proliferation, survival and cell death. Research focused on the pathogenesis of plexiform neurofibroma and biology of NF1 and their malignant peripheral nerve sheath tumors has identified potential goals including Ras it self, Raf kinase, angiogenesis, growth factor receptors, and mammalian target of rapamycin. For instance, S6K1 is activated in MPSNT cells with NF1 mutations, and this response is attenuated by rapamycin in MPNST cell lines, MPNST xenografts, and in a genetic engineered mouse model. In a mouse sarcoma type in which Nf1 and p53 mutations are in cis on mouse chromosome 11, delayed tumor formation was shown by mice treated with rapamycin. With this foundation, a Phase II trial of rapamycin in plexiform neurofibromas is ongoing. We developed the Nf1flox/flox,DhhCre neurofibroma mouse model where lack of both Nf1 alleles in developing Schwann mobile precursors at embryonic day 12. 5 causes Metastasis neurofibroma development in adult rats. The tumors show the increasing loss of mast cell accumulation, axon Schwann cell interaction, and fibrosis, that are characteristics of human plexiform neurofibromas. Four 20 cancers arise in each mouse and at sacrifice each tumefaction is 10 mm3. We reasoned that MRI with volumetric analysis might be used to monitor neurofibroma growth in the Nf1flox/flox,DhhCre mouse model. According to prior reports implicating mTOR signaling and Raf signaling in NF1 mutant cells, we examined the therapeutic impact of the rapamycin analog RAD001, an mTOR inhibitor, GW9508 885101-89-3 and Sorafenib, a multi-targeted kinase inhibitor that was initially designed as a raf kinase inhibitor, within this model. We show that volumetric MRI can be used to monitor neurofibroma growth in mice. We also show that RAD001 doesn’t minimize neurofibroma progress, while Sorafenib has significant therapeutic impact on some neurofibromas in this model. Methods Mouse We located rats in temperature and humidity controlled services on the 12 hour dark light cycle with free access to food and water as described previously. The animal care and use committee of Cincinnati Kids s Hospital Medical Center permitted all animal use. The mice were in a mixed C57/129/FVBN strain history and were interbred to acquire the expected genotype. Mouse genotyping is described. Vehicle company and substances RAD001 were received from Novartis Pharmaceuticals Corporation. RAD001 was in a solvent that was diluted to 3 parts 2% carboxyl methylcellulose and 2 parts 6% captisol for in vivo usage. Sorafenib was purchased from LC Laboratories. Sorafenib was dissolved in 50% cremophor EL 50% ethanol.