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Supportive Care in Cancer
Published in: Supportive Care in Cancer 8/2018

01-08-2018 | Original Article

Text mining-based in silico drug discovery in oral mucositis caused by high-dose cancer therapy

Authors: Jon Kirk, Nirav Shah, Braxton Noll, Craig B. Stevens, Marshall Lawler, Farah B. Mougeot, Jean-Luc C. Mougeot

Published in: Supportive Care in Cancer | Issue 8/2018

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Abstract

Introduction

Oral mucositis (OM) is a major dose-limiting side effect of chemotherapy and radiation used in cancer treatment. Due to the complex nature of OM, currently available drug-based treatments are of limited efficacy.

Objectives

Our objectives were (i) to determine genes and molecular pathways associated with OM and wound healing using computational tools and publicly available data and (ii) to identify drugs formulated for topical use targeting the relevant OM molecular pathways.

Methods

OM and wound healing-associated genes were determined by text mining, and the intersection of the two gene sets was selected for gene ontology analysis using the GeneCodis program. Protein interaction network analysis was performed using STRING-db. Enriched gene sets belonging to the identified pathways were queried against the Drug-Gene Interaction database to find drug candidates for topical use in OM.

Results

Our analysis identified 447 genes common to both the “OM” and “wound healing” text mining concepts. Gene enrichment analysis yielded 20 genes representing six pathways and targetable by a total of 32 drugs which could possibly be formulated for topical application. A manual search on ClinicalTrials.​gov confirmed no relevant pathway/drug candidate had been overlooked. Twenty-five of the 32 drugs can directly affect the PTGS2 (COX-2) pathway, the pathway that has been targeted in previous clinical trials with limited success.

Conclusions

Drug discovery using in silico text mining and pathway analysis tools can facilitate the identification of existing drugs that have the potential of topical administration to improve OM treatment.
Appendix
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Metadata
Title
Text mining-based in silico drug discovery in oral mucositis caused by high-dose cancer therapy
Authors
Jon Kirk
Nirav Shah
Braxton Noll
Craig B. Stevens
Marshall Lawler
Farah B. Mougeot
Jean-Luc C. Mougeot
Publication date
01-08-2018
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 8/2018
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-018-4096-2

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