A network-based data integration approach to support drug repurposing and multi-Target therapies in triple negative breast cancer

Francesca Vitali, Laurie D. Cohen, Andrea Demartini, Angela Amato, Vincenzo Eterno, Alberto Zambelli, Riccardo Bellazzi

Research output: Contribution to journalArticlepeer-review

Abstract

The integration of data and knowledge from heterogeneous sources can be a key success factor in drug design, drug repurposing and multi-Target therapies. In this context, biological networks provide a useful instrument to highlight the relationships and to model the phenomena underlying therapeutic action in cancer. In our work, we applied network-based modeling within a novel bioinformatics pipeline to identify promisingmulti-Target drugs. Given a certain tumor type/subtype, we derive a disease-specific Protein-Protein Interaction (PPI) network by combining different data-bases and knowledge repositories. Next, the application of suitable graph-based algorithms allows selecting a set of potentially interesting combinations of drug targets. A list of drug candidates is then extracted by applying a recent data fusion approach based on matrix tri-factorization.Available knowledge about selected drugs mechanisms of action is finally exploited to identify the most promising candidates for planning in vitro studies.We applied this approach to the case of Triple Negative Breast Cancer (TNBC), a subtype of breast cancer whose biology is poorly understood and that lacks of specific molecular targets. Our "in-silico" findings have been confirmedby a number of in vitro experiments, whose results demonstrated the ability of the method to select candidates for drug repurposing.

Original languageEnglish
Article numbere0162407
JournalPLoS One
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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