The dual HDAC/PI3K inhibitor CUDC-907 inhibits the growth and proliferation of MYC-driven Group 3 medulloblastoma.

ABSTRACT: Metastatic Group 3 medulloblastoma (G3 MB) have been shown in several studies to be very high risk, particularly those harboring MYC amplification. More effective therapies are especially important for these patients. CUDC-907, a novel dual inhibitor targeting the MYC upstream pathway (HDAC/PI3K), shows significant antitumor efficacy across multiple cancer types. However, the antitumor effects and underlying mechanisms of CUDC-907 in MB, particularly in very high-risk MB, remain unexplored. In this study, we showed that MYC amplified G3 MB cells, patient-derived organoids and xenograft models were sensitive to CUDC-907. CUDC-907 inhibited MYC expression through the HDAC and PI3K pathways, and then induced G0/G1 phase arrest through the MYC-P21/P27-CDKs/cyclins axis. Furthermore, when CUDC-

SUBMITTER: Gou P 

PROVIDER: S-EPMC11997184 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature