ArticleCancer research2022
Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- CAR-T cell therapy: potential for paediatric brain tumours-an update.Journal of neuro-oncology · 2026Review
- Phylogeography of Bone Metastasis: Clonal Evolution, Skeletal Niche Adaptation, and Clinical Implications.International journal of molecular sciences · 2026Review
- From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- Medulloblastoma stem cell programs: Molecular roadmaps of disease progression.Developmental cell · 2026Review
- Appraisal of CRISPR Technology as an Innovative Screening to Therapeutic Toolkit for Genetic Disorders.Molecular biotechnology · 2026Review
- Single-cell multi-omics identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma.Nature communications · 2025Article
- The transcription factor LHX2 mediates and enhances oncogenic BMP signaling in medulloblastoma.Cell death and differentiation · 2025Article
- Systematic decoding of functional enhancer connectomes and risk variants in human glioma.Nature cell biology · 2025Article
- Identification of a small molecule targeting EPLIN as a novel strategy for the treatment of pediatric neuroblastoma and medulloblastoma.Cell death & disease · 2025Article
- EZH2 inhibitor and Vismodegib synergistically inhibit the growth and metastasis of medulloblastoma.Medical oncology (Northwood, London, England) · 2025Article
- SOX9: a novel janus-faced regulator in immunity and its promise as a therapeutic target.Frontiers in molecular biosciences · 2025Review
- LncRNA-Mediated TPI1 and PKM2 Promote Self-Renewal and Chemoresistance in GBM.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies.Cancers · 2024Review
- Drivers Underlying Metastasis and Relapse in Medulloblastoma and Targeting Strategies.Cancers · 2024Review
- Review
- Review
- SOX9 drives KRAS-induced lung adenocarcinoma progression and suppresses anti-tumor immunity.Oncogene · 2023Article
- YB1 modulates the DNA damage response in medulloblastoma.Scientific reports · 2023Article
- ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors.Nature communications · 2023Article
- Quiescent Cancer Cells-A Potential Therapeutic Target to Overcome Tumor Resistance and Relapse.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
36 authors at 6 institutions in 4 countries.
Funding
Abstract
Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse. SIGNIFICANCE: SOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.