419PD - Strong Additive Effect of Everolimus and Octreotide or Pasireotide on Meningioma Cells in Vitro: A New Therapeutic Strategy for These Tumors

Abstract

ABSTRACT Disclosure A. Barlier: the research prgramm was partially supported by Novartis. All other authors have declared no conflicts of interest. Meningiomas are the most frequent brain tumors after 35 years-old. When total surgical removal is not possible, radiotherapy and radiosurgery are able to control tumoral growth in some cases. But no chemotherapy has ever been demonstrated to be really efficient. Then, in cases of recurrence (particularly in WHO grade 2 and 3 meningiomas), no therapeutic exist at present, leading to fatal issue. Pi3Kinase-Akt-mTor pathway is activated in meningiomas, due to Merlin protein (encoded by NF2 gene) inactivation. SST2 somatostatin receptors are strongly expressed in meningiomas. These receptors are targeted by somatostatin agonists (octreotide and a new “pan-sst” agonist, pasireotide) which antiproliferative effect is known in other types of tumors. The aim of our study is to test in vitro effects of m-Tor inhibitor (Everolimus) and/or somatostatin agonists Octreotide or pasireotide, on human meningiomas in primary culture. By real time PCR, we found that sst2 was expressed in all meningiomas. The expression level of Merlin was highly variable between tumors and was inversely correlated with mTor pathway activation (p