Comer, Charley;
Cotton, Kian;
Edwards, Christopher;
Dai, Xiaoyang;
Badodi, Sara;
Buccafusca, Roberto;
Bennett, Chris;
... Niklison-Chirou, Maria Victoria; + view all
(2025)
Simvastatin suppresses spinal cord metastasis of medulloblastoma at clinically significant doses.
Cell Death & Disease
, 16
(1)
, Article 527. 10.1038/s41419-025-07829-0.
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Abstract
Medulloblastomas (MBs) are aggressive brain cancers and represent the most common primary malignant tumour in children. Current treatment protocols involve an intensive regimen of surgery, radiation therapy and chemotherapy, guided by histopathology and risk stratification. Unfortunately, disease relapse proves fatal in 30% of cases, and treatment efficacy is compromised as MB cells develop resistance. Therefore, there is a critical need for more effective and tolerable therapies, especially for the treatment of aggressive MBs associated with a poor prognosis. Lipid metabolism reprogramming, characterized by increased cholesterol synthesis, lipid uptake and the activation of de novo lipogenesis, is a newly identified hallmark of cancers. Cholesterol is an essential structural component of membranes that contributes to membrane integrity and fluidity. Recently, increasing evidence has indicated that cholesterol is a major determinant by modulating cell signalling events governing the hallmarks of cancer. Our research demonstrates there is an overexpression of cholesterol metabolism in group 3 (G3), and group 4 (G4) MB subgroups compared to Sonic Hedgehog (SHH)-MB subgroup. In these tumours, cholesterol metabolism supports cell migration through the Rho-GTPase signalling pathway. Notably, we observed that shifting the culture conditions from 2D to 3D significantly upregulates lipid metabolism. Furthermore, spheroids derived from G3/G4-MBs and SHH-MBs show similar sensitivity to low doses of simvastatin. We validated these findings in a xenograft mouse model, where treatment with low doses of simvastatin led to increased survival time and remarkably, also reduced the metastatic spread of MB cells to the spinal cord. These results suggest that simvastatin holds potential as an adjuvant treatment for patients with medulloblastoma.
| Type: | Article |
|---|---|
| Title: | Simvastatin suppresses spinal cord metastasis of medulloblastoma at clinically significant doses |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41419-025-07829-0 |
| Publisher version: | https://doi.org/10.1038/s41419-025-07829-0 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, CENTRAL-NERVOUS-SYSTEM, MEVALONATE PATHWAY, TUMOR BIOLOGY, CANCER, CLASSIFICATION, ORGANIZATION, RELEVANCE, STATINS, GTPASES, RHO |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10219682 |
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