ArticleCancers2021
Connectivity Map Analysis Indicates PI3K/Akt/mTOR Inhibitors as Potential Anti-Hypoxia Drugs in Neuroblastoma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- DBSCAN and DBCV application to open medical records heterogeneous data for identifying clinically significant clusters of patients with neuroblastoma.BioData mining · 2025Article
- Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research.Molecular neurobiology · 2025Review
- Integrated pan-cancer analysis revealed therapeutic targets in the ABC transporter protein family.PloS one · 2025Article
- A pan-cancer analysis of anti-proliferative protein family genes for therapeutic targets in cancer.Scientific reports · 2023Article
- Retinoic Acid Receptor Is a Novel Therapeutic Target for Postoperative Cognitive Dysfunction.Pharmaceutics · 2023Article
- Transcriptome from Paired Samples Improves the Power of Comprehensive COVID-19 Host-Viral Characterization.International journal of molecular sciences · 2023Article
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- Integrated analysis reveals effects of bioactive ingredients fromFrontiers in plant science · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma (NB) is one of the deadliest pediatric cancers, accounting for 15% of deaths in childhood. Hypoxia is a condition of low oxygen tension occurring in solid tumors and has an unfavorable prognostic factor for NB. In the present study, we aimed to identify novel promising drugs for NB treatment. Connectivity Map (CMap), an online resource for drug repurposing, was used to identify connections between hypoxia-modulated genes in NB tumors and compounds. Two sets of 34 and 21 genes up- and down-regulated between hypoxic and normoxic primary NB tumors, respectively, were analyzed with CMap. The analysis reported a significant negative connectivity score across nine cell lines for 19 compounds mainly belonging to the class of PI3K/Akt/mTOR inhibitors. The gene expression profiles of NB cells cultured under hypoxic conditions and treated with the mTORC complex inhibitor PP242, referred to as the Mohlin dataset, was used to validate the CMap findings. A heat map representation of hypoxia-modulated genes in the Mohlin dataset and the gene set enrichment analysis (GSEA) showed an opposite regulation of these genes in the set of NB cells treated with the mTORC inhibitor PP242. In conclusion, our analysis identified inhibitors of the PI3K/Akt/mTOR signaling pathway as novel candidate compounds to treat NB patients with hypoxic tumors and a poor prognosis.
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