Antiproliferative and Antimigratory Effects of mTOR Inhibitors in Paediatric Low-grade Gliomas Models. A Comparison between Rapamycin and Sapanisertib

Low-grade gliomas (LGG) are the most common brain tumors in children. Surgical resection followed by chemo-radiotherapy currently remains the optimal treatment although many tumors are not suitable for surgical intervention and/or they do progress despite conventional chemotherapy. Considering the significant role of the mTOR signalling pathway in carcinogenesis and glioma progression, extensive efforts have been dedicated to counteracting its hyperactivation in cancer cells, leading to the development of various mTOR inhibitors for cancer treatment. This study aimed to investigate the effects of two mTOR inhibitors (Rapamycin and Sapanisertib) on cell viability, toxicity and tumor invasiveness in two well-established human paediatric low-grade glioma models. Our data show that mTOR inhibitors are effective in reducing the proliferation of both RES 186 and 259 cell lines. However, after long-term treatments an activation of MAPK kinase pathway occurs. In addition RAPA and SAP are able to reduce cell migration, through the reduction of Nf-Kb and S6 protein. Some differences emerged between the drugs. Sapanisertib was found to be more effective than rapamycin, as antiproliferative but not as antimigratory drug.