Abstract
INTRODUCTION: To date, no drug has clearly demonstrated its efficacy in aggressive and recurrent meningiomas. We have previously demonstrated the interest of the combination of octreotide (somatostatin agonist) and everolimus (mTOR inhibitor) in meningiomas, allowing the establishment of a clinical trial. The pasireotide is a pansomatostatin agonist targeting SST1, SST2, SST3 and SST5 receptors while octreotide only targets SST2 receptor. Pasireotide is more stable than octreotide and allows a different mode of SST2 receptors internalization, increasing SST2 membrane expression. In other types of tumors (pituitary adenomas and neuroendocrine tumors), a better effect of pasireotide compared to octreotide has been demonstrated. The aim of this in vitro study is to compare the effect of pasireotide and octreotide alone or in combination with everolimus to determine the potential interest of a clinical trial with pasireotide-everolimus. MATERIAL AND METHODS: The expression of SST receptors was analyzed by real-time PCR. The impact of drugs on cell viability and on the PI3K- Akt-mTOR pathway was analyzed in 70 tumors placed in primary culture immediately after surgical resection. RESULTS: SST2 is expressed in the 30 tumors tested, SST1 in 40.5% and in 35% SST5. Among 48 analyzed tumors, anti-proliferative effect of pasireotide was stronger compared to octreotide and appears related to the expression of SST1. Pasireotide quite provides a stronger inhibitory effect on the PI3K-Akt and on the cell-cycle proteins compared to octreotide. The additive effect of the combination pasireotide-everolimus is more powerful than the combination octreotide-everolimus. CONCLUSION: All our in vitro results underline the importance of pasireotide-everolimus vs. octreotide-everolimus combination, suggesting clinical interest for aggressive meningiomas.