Research And Grants

Targeting Metabolic Vulnerabilities for Treating Medulloblastoma

Medulloblastoma is the most common type of pediatric brain cancer, which accounts for >10% of all childhood cancer deaths. Despite the progress in treating medulloblastoma, the 5-year survival rate for high-risk tumors remains poor and the risk of recurrence within two years of treatment is still high. This is mainly due to the presence of Medulloblastoma Stem Cells (MBSCs) that self-renew themselves and render patients resistant to radiation that is routinely used to treat medulloblastoma patients. In this proposal, we provide compelling evidence that S-phase kinase-associated protein 2 (SKP2) may be one of the critical proteins that supports MBSCs.  Our preliminary results suggest that SKP2 promotes MBSCs growth and radiation resistance by supporting the energy needs of MBSCs. In this application, we propose to disrupt these energy-generating pathways to not only block medulloblastoma growth but also improve the efficacy of radiation therapy. Importantly, our study will provide a strong rationale to initiate clinical trials with glutaminase inhibitor CB-839, which is in clinical trial for treating adult brain cancers, alone or in combination with radiation for treating medulloblastoma patients without any delay.