title: A Network-Based Data Integration Approach to Support Drug Repurposing and Multi-Target Therapies in Triple Negative Breast Cancer.
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 promising multi-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 confirmed by a number of in vitro experiments, whose results demonstrated the ability of the method to select candidates for drug repurposing.
authors.affiliation: Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Pavia, Italy.
authors.forename: Francesca
authors.identifier: http://orcid.org/0000-0003-2916-6402
authors.initials: F
authors.lastname: Vitali
authors.affiliation: Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Pavia, Italy.
authors.forename: Laurie D
authors.initials: LD
authors.lastname: Cohen
authors.affiliation: Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Demartini
authors.affiliation: IRCCS-Fondazione S. Maugeri, Pavia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Amato
authors.affiliation: IRCCS-Fondazione S. Maugeri, Pavia, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Eterno
authors.affiliation: IRCCS-Fondazione S. Maugeri, Pavia, Italy.|Oncologia Medica, ASST Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zambelli
authors.affiliation: Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Pavia, Italy.|IRCCS-Fondazione S. Maugeri, Pavia, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bellazzi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008962:Models, Theoretical; D009010:Monte Carlo Method; D018511:Systems Integration; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents