ArticleOncotarget2016
Computational drugs repositioning identifies inhibitors of oncogenic PI3K/AKT/P70S6K-dependent pathways among FDA-approved compounds.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
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- The ELAVL3/MYCN positive feedback loop provides a therapeutic target for neuroendocrine prostate cancer.Nature communications · 2023Article
- Computational drug repurposing of Akt-1 allosteric inhibitors for non-small cell lung cancer.Scientific reports · 2023Article
- Identification of Promising Drug Candidates against Prostate Cancer through Computationally-Driven Drug Repurposing.International journal of molecular sciences · 2023Article
- Double Repositioning: Veterinary Antiparasitic to Human Anticancer.International journal of molecular sciences · 2022Review
- Identification of potential biological targets of oxindole scaffolds viaF1000Research · 2022Article
- Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer.Cancers · 2021Article
- Article
- Pyrvinium pamoate inhibits cell proliferation through ROS-mediated AKT-dependent signaling pathway in colorectal cancer.Medical oncology (Northwood, London, England) · 2021Article
- High-Throughput Screen of Natural Compounds and Biomarkers for NSCLC Treatment by Differential Expression and Weighted Gene Coexpression Network Analysis (WGCNA).BioMed research international · 2021Article
- High-ThroughputFrontiers in oncology · 2021Article
- Drug Repurposing for Triple-Negative Breast Cancer.Journal of personalized medicine · 2020Review
- Pyrvinium Pamoate Induces Death of Triple-Negative Breast Cancer Stem-Like Cells and Reduces Metastases through Effects on Lipid Anabolism.Cancer research · 2020Article
- Targeting the CK1α/CBX4 axis for metastasis in osteosarcoma.Nature communications · 2020Article
- Pyrvinium Pamoate Use in a B cell Acute Lymphoblastic Leukemia Model of the Bone Tumor Microenvironment.Pharmaceutical research · 2020Article
- High-Throughput Transcriptome Profiling in Drug and Biomarker Discovery.Frontiers in genetics · 2020Review
- Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map.Molecules (Basel, Switzerland) · 2019Article
- Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A pre-clinical assessment.Journal of cellular physiology · 2018Article
- Drug repurposing for the treatment of glioblastoma multiforme.Journal of experimental & clinical cancer research : CR · 2017Review
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The discovery of inhibitors for oncogenic signalling pathways remains a key focus in modern oncology, based on personalized and targeted therapeutics. Computational drug repurposing via the analysis of FDA-approved drug network is becoming a very effective approach to identify therapeutic opportunities in cancer and other human diseases. Given that gene expression signatures can be associated with specific oncogenic mutations, we tested whether a "reverse" oncogene-specific signature might assist in the computational repositioning of inhibitors of oncogenic pathways. As a proof of principle, we focused on oncogenic PI3K-dependent signalling, a molecular pathway frequently driving cancer progression as well as raising resistance to anticancer-targeted therapies. We show that implementation of "reverse" oncogenic PI3K-dependent transcriptional signatures combined with interrogation of drug networks identified inhibitors of PI3K-dependent signalling among FDA-approved compounds. This led to repositioning of Niclosamide (Niclo) and Pyrvinium Pamoate (PP), two anthelmintic drugs, as inhibitors of oncogenic PI3K-dependent signalling. Niclo inhibited phosphorylation of P70S6K, while PP inhibited phosphorylation of AKT and P70S6K, which are downstream targets of PI3K. Anthelmintics inhibited oncogenic PI3K-dependent gene expression and showed a cytostatic effect in vitro and in mouse mammary gland. Lastly, PP inhibited the growth of breast cancer cells harbouring PI3K mutations. Our data indicate that drug repositioning by network analysis of oncogene-specific transcriptional signatures is an efficient strategy for identifying oncogenic pathway inhibitors among FDA-approved compounds. We propose that PP and Niclo should be further investigated as potential therapeutics for the treatment of tumors or diseases carrying the constitutive activation of the PI3K/P70S6K signalling axis.
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