AccScience Publishing / ITPS / Online First / DOI: 10.36922/itps.2571
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SHORT COMMUNICATION

In silico analysis for drug repurposing in cholesteatoma: A novel approach to address an unmet medical need

Ioannis M. Vlastos1* ,  Mohannad Almomani1 ,  John Hajiioannou2 ,  Nikolaos Drimalas1 ,  Kalliopi Gkouskou3
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1 Department of Otolaryngology-Head and Neck Surgery, Evangelismos Hospital, Athens, Greece
2 Department of Otolaryngology-Head and Neck Surgery, Medical School and University Hospital of Thessalia, Larissa, Greece
3 Biology and Genetics Lab, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
INNOSC Theranostics and Pharmacological Sciences, 2571 https://doi.org/10.36922/itps.2571
Submitted: 29 December 2023 | Revised: 17 February 2024 | Accepted: 20 March 2024 | Published: 11 April 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Cholesteatoma presents a significant clinical challenge with limited pharmaceutical treatment options. This paper aims to explore the potential of drug repurposing for managing cholesteatoma through advanced bioinformatics analysis of high-throughput genetic data. For this purpose, we conducted a systematic search of published high-throughput genetic studies related to cholesteatoma and used functional and literature enrichment analysis of multiple sets, a validated web-based bioinformatics platform, for analysis. We employed common pathway enrichment analysis and cross-referenced data from DrugBank and gene list automatically derived for you drug annotations to identify potential medical treatments. Our analysis covered eight high-throughput genetic studies, with extended gene lists available for five of them. Enrichment analysis identified common pathways, including matrix metalloproteinases, interleukins, apoptosis, and the phosphoinositide 3-kinase-AKT pathway, shedding light on both expected and less-studied aspects of cholesteatoma pathogenesis. In addition, the analysis proposed several medications, including anti-tumor necrosis factor-α (TNF-α), zinc, and marimastat, as potential treatments. In conclusion, drug repurposing is a potential cost-effective approach to address the unmet medical need for cholesteatoma management. The identified medications, especially anti-TNFα and zinc, offer promising options. Given the limited research funding in this field, this bioinformatic approach holds great promise, highlighting specific molecular pathways that hold the greatest potential to be implicated in the pathogenesis of cholesteatoma and offering a faster route for future trials to reduce cholesteatoma recurrence.

Keywords
Cholesteatoma
Enrichment pathways
Drug repurposing
Bioinformatics platform
Funding
None.
Conflict of interest
The authors declare no conflict of interest.
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Print ISSN: 2705-0734, Published by AccScience Publishing
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