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Network integration of multi-tumour omics data suggests novel targeting strategies.
- Source :
-
Nature communications [Nat Commun] 2018 Oct 30; Vol. 9 (1), pp. 4514. Date of Electronic Publication: 2018 Oct 30. - Publication Year :
- 2018
-
Abstract
- We characterize different tumour types in search for multi-tumour drug targets, in particular aiming for drug repurposing and novel drug combinations. Starting from 11 tumour types from The Cancer Genome Atlas, we obtain three clusters based on transcriptomic correlation profiles. A network-based analysis, integrating gene expression profiles and protein interactions of cancer-related genes, allows us to define three cluster-specific signatures, with genes belonging to NF-κB signaling, chromosomal instability, ubiquitin-proteasome system, DNA metabolism, and apoptosis biological processes. These signatures have been characterized by different approaches based on mutational, pharmacological and clinical evidences, demonstrating the validity of our selection. Moreover, we define new pharmacological strategies validated by in vitro experiments that show inhibition of cell growth in two tumour cell lines, with significant synergistic effect. Our study thus provides a list of genes and pathways that could possibly be used, singularly or in combination, for the design of novel treatment strategies.
- Subjects :
- Apoptosis genetics
Chromosomal Instability genetics
DNA metabolism
Drug Repositioning
Genes, Neoplasm
High-Throughput Screening Assays
Humans
Molecular Targeted Therapy
NF-kappa B genetics
NF-kappa B metabolism
Neoplasms genetics
Neoplasms metabolism
Proteasome Endopeptidase Complex genetics
Proteasome Endopeptidase Complex metabolism
Signal Transduction
Transcriptome
Ubiquitin genetics
Ubiquitin metabolism
Gene Regulatory Networks
Genomics
Neoplasms drug therapy
Protein Interaction Maps
Proteomics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 30375513
- Full Text :
- https://doi.org/10.1038/s41467-018-06992-7