ArticleActa neuropathologica communications2014
WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.
Article in Acta neuropathologica communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Lithium for Radiation-Induced Damage in Pediatric Brain Tumors: Preclinical Evidence and Clinical Perspectives.Journal of clinical medicine · 2026Review
- High-dose chemotherapy with autologous stem cell rescue in children under 5 years of age with central nervous system embryonal tumors: results from a prospective cohort in an upper-middle-income country.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Potential neuroprotective and therapeutic agents and their mechanisms for irradiation-induced brain injury.Ibrain · 2026Review
- Bioengineered mPCL scaffolds with LiCl-stimulated hPDLCs cell sheets for enhanced periodontal regeneration.Clinical oral investigations · 2025Article
- Depression and Anxiety After Radiation-Induced Brain Injury: A Review of Current Research Progress.Current oncology (Toronto, Ont.) · 2025Review
- Genomic predictors of radiation response: recent progress towards personalized radiotherapy for brain metastases.Cell death discovery · 2024Review
- Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies.Cancers · 2024Review
- Irradiation and lithium treatment alter the global DNA methylation pattern and gene expression underlying a shift from gliogenesis towards neurogenesis in human neural progenitors.Translational psychiatry · 2023Article
- Lithium: A Promising Anticancer Agent.Life (Basel, Switzerland) · 2023Review
- Co-occurring KEAP1 and TP53 mutations in lung squamous cell carcinoma induced primary resistance to thoracic radiotherapy: A case report.Thoracic cancer · 2023Article
- Review
- Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Review
- A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature.Neurology international · 2021Review
- Lithium treatment reverses irradiation-induced changes in rodent neural progenitors and rescues cognition.Molecular psychiatry · 2021Article
- Drug Repurposing in Medulloblastoma: Challenges and Recommendations.Current treatment options in oncology · 2020Review
- Wnt activation as a therapeutic strategy in medulloblastoma.Nature communications · 2020Article
- Review
- NPI-0052 and γ-radiation induce a synergistic apoptotic effect in medulloblastoma.Cell death & disease · 2019Article
- Systems Biology Understanding of the Effects of Lithium on Cancer.Frontiers in oncology · 2019Article
- TP53 Mutation, MYCN Amplification, and Large Cell/Anaplastic Histology in Medulloblastoma.Indian journal of pediatrics · 2018Article
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Authors and funding
60 authors at 20 institutions in 13 countries.
Funding
Abstract
TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
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