ArticleScience translational medicine2018
Systems biology-based drug repositioning identifies digoxin as a potential therapy for groups 3 and 4 medulloblastoma.
Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
- Establishing a Clinically Relevant Radiation Therapy Method for Preclinical Medulloblastoma Research.Advances in radiation oncology · 2026Article
- Targeting Pediatric Glioblastomas by Combining OLIG2 Inhibitor CT-179 with Fractionated Radiation in a Panel of Patient-Derived Orthotopic Xenograft Mouse Models.International journal of molecular sciences · 2026Article
- Repurposing Acebutolol for Osteoporosis Treatment: Insights From Multi-Omics and Multi-Modal Data Analysis.Clinical pharmacology and therapeutics · 2025Article
- Targeting Ion Channels: Blockers Suppress Calcium Signals and Induce Cytotoxicity Across Medulloblastoma Cell Models.Bioengineering (Basel, Switzerland) · 2025Article
- Integrating pharmacogenomics and cheminformatics with diverse disease phenotypes for cell type-guided drug discovery.Genome medicine · 2025Article
- Identification and therapeutic investigation of biomarker genes underpinning hepatocellular carcinoma: anFrontiers in bioinformatics · 2025Article
- An In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Levosimendan: Potential Drug Repurposing for Cervical Cancer.Current issues in molecular biology · 2024Article
- Article
- Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations.Cancers · 2024Review
- Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models.Journal of translational medicine · 2023Article
- Rewiring Drug Research and Development through Human Data-Driven Discovery (HDPharmaceutics · 2023Review
- Interactions between driver genes shape the signaling pathway landscape and direct hepatocellular carcinoma therapy.Cancer science · 2023Article
- Guiding Drug Repositioning for Cancers Based on Drug Similarity Networks.International journal of molecular sciences · 2023Article
- Review
- Epigenetic Alterations of Repeated Relapses in Patient-matched Childhood Ependymomas.Nature communications · 2022Article
- Network-Based Analysis to Identify Hub Genes Involved in Spatial Root Response to Mechanical Constrains.Cells · 2022Article
- Evaluation of an EZH2 inhibitor in patient-derived orthotopic xenograft models of pediatric brain tumors alone and in combination with chemo- and radiation therapies.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Digoxin Ameliorates Glymphatic Transport and Cognitive Impairment in a Mouse Model of Chronic Cerebral Hypoperfusion.Neuroscience bulletin · 2022Article
- Converging multi-modality datasets to build efficient drug repositioning pipelines against Alzheimer's disease and related dementias.Medical review (2021) · 2022Article
- Artificial intelligence unifies knowledge and actions in drug repositioning.Emerging topics in life sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Although outcomes have improved in recent decades, new treatments are still needed to improve survival and reduce treatment-related complications. The MB subtypes groups 3 and 4 represent a particular challenge due to their intragroup heterogeneity, which limits the options for "rational" targeted therapies. Here, we report a systems biology approach to drug repositioning that integrates a nonparametric, bootstrapping-based simulated annealing algorithm and a 3D drug functional network to characterize dysregulated driver signaling networks, thereby identifying potential drug candidates. From more than 1300 drug candidates studied, we identified five members of the cardiac glycoside family as potentially inhibiting the growth of groups 3 and 4 MB and subsequently confirmed this in vitro. Systemic in vivo treatment of orthotopic patient-derived xenograft (PDX) models of groups 3 and 4 MB with digoxin, a member of the cardiac glycoside family approved for the treatment of heart failure, prolonged animal survival at plasma concentrations known to be tolerated in humans. These results demonstrate the power of a systematic drug repositioning method in identifying a potential treatment for MB. Our strategy could potentially be used to accelerate the repositioning of treatments for other human cancers that lack clearly defined rational targets.
Indexed as
Identifiers
What OpenQuestion holds
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.