ArticleJournal of the American Medical Informatics Association : JAMIA2016
A network-based drug repositioning infrastructure for precision cancer medicine through targeting significantly mutated genes in the human cancer genomes.
Article in Journal of the American Medical Informatics Association : JAMIA, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
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- Cancer network pharmacology: multi-network regulatory mechanisms and future directions.Medical oncology (Northwood, London, England) · 2025Review
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- Artificial intelligence in cancer target identification and drug discovery.Signal transduction and targeted therapy · 2022Review
- A drug repositioning algorithm based on a deep autoencoder and adaptive fusion.BMC bioinformatics · 2021Article
- Abnormal spindle-like microcephaly-associated protein enhances cell invasion through Wnt/β-catenin-dependent regulation of epithelial-mesenchymal transition in non-small cell lung cancer cells.Journal of thoracic disease · 2021Article
- Overexpression of abnormal spindle-like microcephaly-associated (ASPM) increases tumor aggressiveness and predicts poor outcome in patients with lung adenocarcinoma.Translational cancer research · 2021Article
- Network-Based Identification and Experimental Validation of Drug Candidates Toward SARS-CoV-2Frontiers in genetics · 2021Article
- A Pan-Cancer Analysis of Transcriptome and Survival Reveals Prognostic Differentially Expressed LncRNAs and Predicts Novel Drugs for Glioblastoma Multiforme Therapy.Frontiers in genetics · 2021Article
- Abnormal spindle-like microcephaly-associated (ASPM) gene expression in posterior fossa brain tumors of childhood and adolescence.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2021Article
- Individualized genetic network analysis reveals new therapeutic vulnerabilities in 6,700 cancer genomes.PLoS computational biology · 2020Article
- Quantitative proteomics analysis of differentially expressed proteins induced by astragaloside IV in cervical cancer cell invasion.Cellular & molecular biology letters · 2020Article
- A genome-wide positioning systems network algorithm for in silico drug repurposing.Nature communications · 2019Article
- A Network Pharmacology Approach for the Identification of Common Mechanisms of Drug-Induced Peripheral Neuropathy.CPT: pharmacometrics & systems pharmacology · 2019Article
- Characterization of Tumor-Suppressor Gene Inactivation Events in 33 Cancer Types.Cell reports · 2019Article
- An Insight Into the Molecular Mechanism of Berberine Towards Multiple Cancer Types Through Systems Pharmacology.Frontiers in pharmacology · 2019Article
- Personal Mutanomes Meet Modern Oncology Drug Discovery and Precision Health.Pharmacological reviews · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveDevelopment of computational approaches and tools to effectively integrate multidomain data is urgently needed for the development of newly targeted cancer therapeutics.
methodsWe proposed an integrative network-based infrastructure to identify new druggable targets and anticancer indications for existing drugs through targeting significantly mutated genes (SMGs) discovered in the human cancer genomes. The underlying assumption is that a drug would have a high potential for anticancer indication if its up-/down-regulated genes from the Connectivity Map tended to be SMGs or their neighbors in the human protein interaction network.
resultsWe assembled and curated 693 SMGs in 29 cancer types and found 121 proteins currently targeted by known anticancer or noncancer (repurposed) drugs. We found that the approved or experimental cancer drugs could potentially target these SMGs in 33.3% of the mutated cancer samples, and this number increased to 68.0% by drug repositioning through surveying exome-sequencing data in approximately 5000 normal-tumor pairs from The Cancer Genome Atlas. Furthermore, we identified 284 potential new indications connecting 28 cancer types and 48 existing drugs (adjusted P < .05), with a 66.7% success rate validated by literature data. Several existing drugs (e.g., niclosamide, valproic acid, captopril, and resveratrol) were predicted to have potential indications for multiple cancer types. Finally, we used integrative analysis to showcase a potential mechanism-of-action for resveratrol in breast and lung cancer treatment whereby it targets several SMGs (ARNTL, ASPM, CTTN, EIF4G1, FOXP1, and STIP1).
conclusionsIn summary, we demonstrated that our integrative network-based infrastructure is a promising strategy to identify potential druggable targets and uncover new indications for existing drugs to speed up molecularly targeted cancer therapeutics.
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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.