PRMT5 as a Potential Therapeutic Target in MYC-Amplified Medulloblastoma

Devendra Kumar; Stuti Jain; Don W Coulter; Shantaram S Joshi; Nagendra K Chaturvedi

doi:10.3390/cancers15245855

PRMT5 as a Potential Therapeutic Target in MYC-Amplified Medulloblastoma

Cancers (Basel). 2023 Dec 15;15(24):5855. doi: 10.3390/cancers15245855.

Authors

Devendra Kumar¹, Stuti Jain¹, Don W Coulter^{1

2

3}, Shantaram S Joshi⁴, Nagendra K Chaturvedi^{1

2

3}

Affiliations

¹ Department of Pediatrics, Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE 69198, USA.
² Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE 69198, USA.
³ Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 69198, USA.
⁴ Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 69198, USA.

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.

Keywords: MYC; PRMT5 inhibitors; SDMA; brain cancer; medulloblastoma.

Publication types

Review

Abstract

Publication types

Grants and funding