ArticleNPJ systems biology and applications2017
Neighbours of cancer-related proteins have key influence on pathogenesis and could increase the drug target space for anticancer therapies.
Article in NPJ systems biology and applications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
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- A bioinformatics approach to elucidate conserved genes and pathways in C. elegans as an animal model for cardiovascular research.Scientific reports · 2024Article
- Chemogenomic library design strategies for precision oncology, applied to phenotypic profiling of glioblastoma patient cells.iScience · 2023Article
- A systems genomics approach to uncover patient-specific pathogenic pathways and proteins in ulcerative colitis.Nature communications · 2022Article
- Construction and contextualization approaches for protein-protein interaction networks.Computational and structural biotechnology journal · 2022Review
- Network Biology Approaches to Achieve Precision Medicine in Inflammatory Bowel Disease.Frontiers in genetics · 2021Review
- Identification of the key target profiles underlying the drugs of narrow therapeutic index for treating cancer and cardiovascular disease.Computational and structural biotechnology journal · 2021Article
- QSAR-derived affinity fingerprints (part 2): modeling performance for potency prediction.Journal of cheminformatics · 2020Article
- Gene relevance based on multiple evidences in complex networks.Bioinformatics (Oxford, England) · 2020Article
- Centrality Analysis of Protein-Protein Interaction Networks and Molecular Docking Prioritize Potential Drug-Targets in Type 1 Diabetes.Iranian journal of pharmaceutical research : IJPR · 2020Article
- Topological integration of RPPA proteomic data with multi-omics data for survival prediction in breast cancer via pathway activity inference.BMC medical genomics · 2019Article
- Integrating gene regulatory pathways into differential network analysis of gene expression data.Scientific reports · 2019Article
- Discrete dynamic network modeling of oncogenic signaling: Mechanistic insights for personalized treatment of cancer.Current opinion in systems biology · 2018Review
- A side-effect free method for identifying cancer drug targets.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Even targeted chemotherapies against solid cancers show a moderate success increasing the need to novel targeting strategies. To address this problem, we designed a systems-level approach investigating the neighbourhood of mutated or differentially expressed cancer-related proteins in four major solid cancers (colon, breast, liver and lung). Using signalling and protein-protein interaction network resources integrated with mutational and expression datasets, we analysed the properties of the direct and indirect interactors (first and second neighbours) of cancer-related proteins, not found previously related to the given cancer type. We found that first neighbours have at least as high degree, betweenness centrality and clustering coefficient as cancer-related proteins themselves, indicating a previously unknown central network position. We identified a complementary strategy for mutated and differentially expressed proteins, where the affect of differentially expressed proteins having smaller network centrality is compensated with high centrality first neighbours. These first neighbours can be considered as key, so far hidden, components in cancer rewiring, with similar importance as mutated proteins. These observations strikingly suggest targeting first neighbours as a novel strategy for disrupting cancer-specific networks. Remarkably, our survey revealed 223 marketed drugs already targeting first neighbour proteins but applied mostly outside oncology, providing a potential list for drug repurposing against solid cancers. For the very central first neighbours, whose direct targeting would cause several side effects, we suggest a cancer-mimicking strategy by targeting their interactors (second neighbours of cancer-related proteins, having a central protein affecting position, similarly to the cancer-related proteins). Hence, we propose to include first neighbours to network medicine based approaches for (but not limited to) anticancer therapies.
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Registered trials
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