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Journal of Translational Medicine

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Open Access 01-12-2018 | Research

In silico identification of drug target pathways in breast cancer subtypes using pathway cross-talk inhibition

Authors: Claudia Cava, Gloria Bertoli, Isabella Castiglioni

Published in: Journal of Translational Medicine | Issue 1/2018

Abstract

Background

Despite great development in genome and proteome high-throughput methods, treatment failure is a critical point in the management of most solid cancers, including breast cancer (BC). Multiple alternative mechanisms upon drug treatment are involved to offset therapeutic effects, eventually causing drug resistance or treatment failure.

Methods

Here, we optimized a computational method to discover novel drug target pathways in cancer subtypes using pathway cross-talk inhibition (PCI). The in silico method is based on the detection and quantification of the pathway cross-talk for distinct cancer subtypes. From a BC data set of The Cancer Genome Atlas, we have identified different networks of cross-talking pathways for different BC subtypes, validated using an independent BC dataset from Gene Expression Omnibus. Then, we predicted in silico the effects of new or approved drugs on different BC subtypes by silencing individual or combined subtype-derived pathways with the aim to find new potential drugs or more effective synergistic combinations of drugs.

Results

Overall, we identified a set of new potential drug target pathways for distinct BC subtypes on which therapeutic agents could synergically act showing antitumour effects and impacting on cross-talk inhibition.

Conclusions

We believe that in silico methods based on PCI could offer valuable approaches to identifying more tailored and effective treatments in particular in heterogeneous cancer diseases.

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Title: In silico identification of drug target pathways in breast cancer subtypes using pathway cross-talk inhibition
Authors: Claudia Cava
Gloria Bertoli
Isabella Castiglioni
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-018-1535-2

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Abstract

Background

Methods

Results

Conclusions

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