Medulloblastoma, which develops in the posterior fossa of the cerebellum, is the most common malignant brain tumor of the pediatric age: in 80% of cases it occurs under the age of 15 years, with an incidence of about 1/200.000. This tumor has a notable tendency to metastasize both in the central nervous system (CNS), in particular in the cerebrospinal fluid and in the meninges, and outside the CNS, as for example in the bone marrow. Conventional therapy consists of surgical resection followed by chemotherapy and radiotherapy, a therapeutic protocol that often involves severe neurocognitive deficiencies. Although recent results have led to a better understanding of the biological basis and pathogenesis of this tumor, much remains to be clarified to improve the prognosis and quality of life of patients.Sporadic medulloblastomas (15-25%) are characterized by mutations that cause an increase in the activity of the Hedgehog signal pathway (Hh), a protein with a key role in the development of the cerebellum and in the processes of neoplastic transformation. The main link between developmental and cancer biology is provided by evidence that stem cells (SC) with similar properties have also been identified in most cancers, including brain cells, the cancer stem cells (CSC). Recent scientific publications suggest that Hh plays a role in determining and maintaining the stem cells of brain cells.Tumor stem cells appear to be candidates in the onset of the disease and constitute an endless reserve for the maintenance and progression of the tumor. The presence of SC within the tumor could also be the factor that can justify the failure of conventional therapy because these cells have characteristics that make them resistant to treatments. Hence, the need to identify new therapeutic strategies that target stem cells to prevent the maintenance and progression of the tumor.Based on the information acquired so far, the project in question aims to study new strategies to make medulloblastoma more sensitive to radiotherapy. In particular, preclinical models will be set up to inhibit, through the in vivo use of RNA interference (RNAi), the gene expression of factors which play a decisive role in the maintenance of pluripotency of embryonic stem cells, to induce differentiation.