Ricerc@Sapienza

Inappropriate activation of the Hedgehog (HH) pathway is responsible for a wide spectrum of cancers including medulloblastoma (MB), the most common and aggressive pediatric brain malignancy. Multi-omics analysis identified four different MB molecular subgroups; HH-MB is the most abundant and genetically understood, making HH signaling an attractive target for the treatment of this tumor. Given the high heterogeneity of MB, the identification of novel players involved in HH signaling regulation is essential to advance innovative and more effective therapeutic approaches. Recently, we identified the aminopeptidase ERAP1 as a strong activator of the HH pathway. In particular, our preliminary findings unveil the oncogenic properties of ERAP1 in HH-MB and demonstrate that its inhibition impairs HH-dependent tumor growth. ERAP1 represents a valuable druggable target for HH-MB clinical management. Thus, the combination of different targeted-drugs, including ERAP1 inhibitors, could be highly effective for HH-MB treatment.
The main goal of this project is to provide a proof-of-principle that targeting ERAP1 in combination with current pharmacological therapies for HH-MB may represent a valuable strategy for MB treatment. Our efforts could open new perspectives for more effective clinical protocols in the treatment of HH-driven tumors.