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Targeting mTOR as a Therapeutic Approach in Medulloblastoma
Mechanistic target of rapamycin (mTOR) is a master signaling pathway that regulates organismal growth and homeostasis, because of its implication in protein and lipid synthesis, and in the control of the cell cycle and the cellular metabolism. Moreover, it is necessary in cerebellar development and stem cell pluripotency maintenance. Its deregulation has been implicated in the medulloblastoma and in medulloblastoma stem cells (MBSCs). Medulloblastoma is the most common malignant solid tumor in childhood. The current therapies have improved the overall survival but they carry serious side effects, such as permanent neurological sequelae and disability. Recent studies have given rise to a new molecular classification of the subgroups of medulloblastoma, specifying 12 different subtypes containing novel potential therapeutic targets. In this review we propose the targeting of mTOR, in combination with current therapies, as a promising novel therapeutic approach.J.A. is recipient of a predoctoral fellowship from the Department of Education of the Basque Government. This work was supported by grants from the Department of Industry of the Basque Government (SAIO13-PC13BN011), and the European Regional Developmental Fund, Institute of Health Carlos III (ISCIII) (PI16/01730) to I.G