biostudies-literatureGou PChongqing Municipal Education Commission Foundation172https://www.ebi.ac.uk/biostudies/studies/S-EPMC11997184biostudies-literatureUnknown11(1)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-Cell death discoveryThe dual HDAC/PI3K inhibitor CUDC-907 inhibits the growth and proliferation of MYC-driven Group 3 medulloblastoma.PMC119971842024WSJK028KJON202300425Gou PLi XXu MZhang DLuo JGan LCui HFang CZhang LLiang PLi MWu XfalseThe dual HDAC/PI3K inhibitor CUDC-907 inhibits the growth and proliferation of MYC-driven Group 3 medulloblastoma.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-2025-01-01T00:00:00Z2025 Apr2026-06-02T04:31:08.905Z2026-04-14T03:13:27.945ZS-EPMC119971844022926010.1038/s41420-025-02470-4