PRMT5 as a Potential Therapeutic Target in MYC-Amplified Medulloblastoma

Simple Summary Medulloblastoma is the most prevalent intracerebellar pediatric brain tumor, accounting for approximately 20% of all childhood brain tumors and over 60% of embryonal brain tumors. MYC-driven medulloblastoma has extreme metastatic potential and is often resistant to multipronged treatment. PRMT5 plays a key role in cell functions and processes in MYC-driven medulloblastoma by stabilizing the MYC protein. RMT5 inhibitors can potentially disrupt MYC's function, impeding tumor progression and offering a target therapeutic approach to treat MYC-amplified medulloblastoma. Here, we highlight the challenges that must be addressed in future drug development.Abstract MYC amplification or overexpression is most common in Group 3 medulloblastomas and is positively associated with poor clinical outcomes. Recently, protein arginine methyltransferase 5 (PRMT5) overexpression has been shown to be associated with tumorigenic MYC functions in cancers, particularly in brain cancers such as glioblastoma and medulloblastoma. PRMT5 regulates oncogenes, including MYC, that are often deregulated in medulloblastomas. However, the role of PRMT5-mediated post-translational modification in the stabilization of these oncoproteins remains poorly understood. The potential impact of PRMT5 inhibition on MYC makes it an attractive target in various cancers. PRMT5 inhibitors are a promising class of anti-cancer drugs demonstrating preclinical and preliminary clinical efficacies. Here, we review the publicly available preclinical and clinical studies on PRMT5 targeting using small molecule inhibitors and discuss the prospects of using them in medulloblastoma therapy.