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Introduction Central nervous system (CNS) tumors are the most frequent solid tumors in the pediatric population ( The WHO grading of gliomas was based on their histological characteristics and natural history and divided them into four grades of malignancy ( Particularly, most pediatric gliomas are low grade (1 and 2) and do not develop into high-grade (3 and 4) tumors as those in adults do ( It has already been established that gliomas follow multiple metabolic strategies to sustain cellular growth ( The insulin and insulin-like growth factor (IGF) system of ligands (IGF1 and IGF2) and receptors (IGF1R and IR) plays important physiological roles to ensure the cellular survival and proliferation of many tissues ( Despite being a transmembrane receptor, intact IGF1R has been detected in the nuclei of human malignant and non-malignant cells ( The present study was designed to explore the role of IGF1R intracellular localization in the biology of pediatric high-grade glioma in vitro and, using subcutaneous xenografts as a proof of concept, by in vivo studies