Network integration of multi-tumour omics data suggests novel targeting strategies

Ítalo Faria do Valle, Giulia Menichetti, Giorgia Simonetti, Samantha Bruno, Isabella Zironi, Danielle Fernandes Durso, José C M Mombach, Giovanni Martinelli, Gastone Castellani, Daniel Remondini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4514
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Oct 30 2018

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Tumors
tumors
Genes
drugs
genes
Neoplasms
Drug Repositioning
signatures
Pharmacology
oncogenes
Biological Phenomena
Chromosomal Instability
genome
Atlases
gene expression
Neoplasm Genes
apoptosis
Cell growth
metabolism
Drug Combinations

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do Valle, Í. F., Menichetti, G., Simonetti, G., Bruno, S., Zironi, I., Durso, D. F., ... Remondini, D. (2018). Network integration of multi-tumour omics data suggests novel targeting strategies. Nature Communications, 9(1), 4514. https://doi.org/10.1038/s41467-018-06992-7

Network integration of multi-tumour omics data suggests novel targeting strategies. / do Valle, Ítalo Faria; Menichetti, Giulia; Simonetti, Giorgia; Bruno, Samantha; Zironi, Isabella; Durso, Danielle Fernandes; Mombach, José C M; Martinelli, Giovanni; Castellani, Gastone; Remondini, Daniel.

In: Nature Communications, Vol. 9, No. 1, 30.10.2018, p. 4514.

Research output: Contribution to journalArticle

do Valle, ÍF, Menichetti, G, Simonetti, G, Bruno, S, Zironi, I, Durso, DF, Mombach, JCM, Martinelli, G, Castellani, G & Remondini, D 2018, 'Network integration of multi-tumour omics data suggests novel targeting strategies', Nature Communications, vol. 9, no. 1, pp. 4514. https://doi.org/10.1038/s41467-018-06992-7
do Valle ÍF, Menichetti G, Simonetti G, Bruno S, Zironi I, Durso DF et al. Network integration of multi-tumour omics data suggests novel targeting strategies. Nature Communications. 2018 Oct 30;9(1):4514. https://doi.org/10.1038/s41467-018-06992-7
do Valle, Ítalo Faria ; Menichetti, Giulia ; Simonetti, Giorgia ; Bruno, Samantha ; Zironi, Isabella ; Durso, Danielle Fernandes ; Mombach, José C M ; Martinelli, Giovanni ; Castellani, Gastone ; Remondini, Daniel. / Network integration of multi-tumour omics data suggests novel targeting strategies. In: Nature Communications. 2018 ; Vol. 9, No. 1. pp. 4514.
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