Ruxolitinib restore chemosensitivity in medulloblastoma resistant cells

Medulloblastoma is one of the most common paediatric brain tumor that develops in the cerebellum, with a five-year overall survival under 60%, despite the several clinical therapies. However, the most relevant challenge is represented by the recurrences that occurs some years later from the first diagnosis and usually are related to chemotherapy resistance. We generated an in vitro model of chemoresistant medulloblastoma and, from different analyses, we found that some pathway are up-regulated in this model, particularly the JAK/STAT signaling pathway. In this thesis we studied the effect of the inhibition of this pathway in medullosblastoma resistant cell lines through the administration of ruxolitinib, an FDA approved JAK inhibitor, in order to overcome the drug resistance and restore the sensitivity of cells to the standard therapy. We have seen that this drug is able to resensitize cells to the chemotherapy, by suppressing anti-apoptotic defense and unlocking pro-aptototic machinery induced by FOXO3a.